Integrated Neuromodulation System for Mood Enhancement of a Living Human Subject

ABSTRACT

The present invention is an ingestable blended formulation which will cause a series of distinct biochemical changes in-vivo; initiate desirable psychological consequences in that person; and induce an observable increase in cognitive functions for that living human subject. In particular, the initiated psychological events will generate a positive change in one&#39;s personal perceptions, evoke optimism as the subjective state of mind, and elicit a more sociable attitude and favorable mood as the observable behavior of the affected human person. Moreover, in addition to the initiation of a more positive state of mind, another major result and effect of ingesting the blended formulation is an observable amplification of human brain functions and a substantive increase of human concentration, focus and memory.

FIELD OF THE INVENTION

The present invention is concerned with the formulation of certainspecifically blended compositions as an integrated neuromodulationsystem and is directed to the use of such blended compositions in-vivoas a food or beverage supplement for initiating positive moodenhancement in a living human subject. In particular, the presentinvention is directed to producing positive mood enhancement through anintegrated system of neuromodulation by concurrently acting uponmultiple naturally occurring neurotransmitter systems which collectivelyresult in a balanced physiologic effect for the individual person.

BACKGROUND OF THE INVENTION The Many Purposes of Medicine

One common concern about the use of cognitive enhancement agents in thebiomedical sphere is that they seemingly go beyond the traditionalpurpose of medicine. A continuing debate exists today over whether it ispossible to draw a clear line of disengagement between a therapeutictreatment and a mere enhancement of ostensibly normal human bodyprocesses and functions; and if so, what is the true difference andmeaningful distinction between them.

Regardless of this ongoing debate, it is nevertheless absolutely clearthat many medicines and medical techniques—such as contraceptivemedication and plastic surgery—constitute enhancements as such; and areovertly employed in a large variety of alternative treatment instanceswhich are not intended to and thus cannot cure, or prevent, or evenameliorate a particular human pathological condition or a diagnosedabnormal circumstance. Moreover, there are also many circumstances andforms of human physiological enhancement that do not easily fit into thetraditional medical model framework, such as psychological techniquesand dietary changes; but which nevertheless are techniques whichunquestionably produce major medical effects. For these reasons, even ifa distinct boundary between therapeutics and enhancements could beagreed upon, it is unclear that such a fixed boundary would have anynormative, much less clinical, significance.

A different, but related, concern is that resorting to medical ortechnological “fixes” will become a displacement for efforts to confrontdeeper social or personal problems. This kind of concern has surfacedrepeatedly with particular regard to the common use of Ritalin and othermedications developed to treat attention-deficit hyperactivity disorder(or “ADHD”). It has been recognized that such medications can functioneffectively as cognitive enhancers in healthy human adults; but theirwidespread abuse in the school-aged child population within the U.S. hassparked fierce debates, with some persons arguing that these medicationsare merely used to paper over the failings of the current publiceducation system (i.e., by making rowdy boys calmer instead ofdeveloping teaching methods that can accommodate a wider range ofindividual learning styles and personal teaching needs).

However, if our modern society requires much more intellectual focusingand concentration than was previously needed by a human child to learnand receive a public school education, then it is certainly no surprisethat many persons of any adult age today struggle regularly not only tomeet the rigorous educational demands of the university andgraduate/professional schools, but also must grapple to satisfy theevermore difficult employment requirements of the adult workplace andcompete to accommodate the ever-changing styles and expectations imposedby the adult social world. Given this perspective, medically inducedmood modifications and the routine use of cognitive enhancement agentsfor mind concentration and sharper mental focus are thus merely oneexemplary extension of the human species' ability to adapt to theunforgiving strains and stresses of his self-created modern lifeenvironment.

Alternative Kinds of Neurotransmitters and their Functions

A. By conventional medical definition, neurotransmitters are thebioactive chemical agents which are released at the axons ending ofneurons at the synapse. More than 60 chemicals substances have beenidentified to date which are postulated to function as neurotransmittersin-vivo.

It is long recognized that different types of neural cells secretealternatives kinds of neurotransmitters. Each neurotransmitter is foundand works in fairly specific CNS anatomical locations; and each has adifferent effect according to what it is and where it is activated.Notably, all of the major neurotransmitter types are made fromparticular amino acids, except for acetycholine.

Characteristically, neurotransmitters are small molecules which actrapidly in-vivo. Typically, each neurotransmitter type is individuallysynthesized within the neuron cytosol at the presynaptic terminals, andare absorbed by active transport into transmitter vesicles in the axonterminal. Then, each time an action potential reaches the presynapticterminal of the neuron, a few vesicles release their neurotransmittercompound into the synaptic cleft; and this act takes only milliseconds(or even less time) to occur. The subsequent release of theseneurotransmitters at the postsynaptic neurons also occurs within amillisecond. The overall effect is to increase or decrease theconductance through ion channels.

B. Neurotransmitters are bioactive compositions which exert their effectby binding to specific receptors on the neuronal postsynaptic membrane.A neurotransmitter can either ‘excite’ its neighboring neuron and soincrease its activity; or ‘inhibit’ its neighboring neuron, therebysuppressing its activity.

In general, the activity of a neuron depends on the balance between thenumber of excitatory and inhibitory processes affecting it, and thesecan occur simultaneously. Most neurotransmitter receptors can be dividedinto two types: ligand-gated receptors and G-protein linked receptors.

Activation of a ligand-gated receptor enables a channel in the receptorto open and permits the influx of chloride and potassium ions into thecell. The positive or negative charges that enter the cell either exciteor inhibit the neuron. Ligands for these receptors include excitatoryneurotransmitters, such as glutamate; and, to a lesser extent,aspartate. Binding of such excitatory ligands to the receptor producesan excitatory postsynaptic potential (EPSP). Alternatively, binding ofinhibitory neurotransmitter ligands, such as GABA and glycine, producesan inhibitory postsynaptic potential (IPSP). Conventionally, theseligand-gated receptors are also known as ionotropic or fast receptors.

G-protein linked receptors are indirectly linked to ion channels, via asecond messenger system involving G-proteins and adenylate cyclase.These receptors are neither precisely excitatory nor inhibitory andmodulate the actions of the classic excitatory and inhibitoryneurotransmitters, such as glutamate and glycine. These receptors tendto have an inhibitory effect if they are linked to the Gi protein in thecell membrane, and exhibit a more excitatory effect if linked to the Gsprotein. G-protein linked receptors are known as metabotropic or slowreceptors; and typical examples include GABA-B, glutamate, dopamine (D1and D2), 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C receptors.

The Different Modes of Action and Functionality for IndividualNeurotransmitters

A. The various kinds of neurotransmitters present alternative modes ofaction, and are typically divided and broadly classified into two broadgroupings, which are:

(i) Excitatory Neurotransmitters: These are exemplified by glutamate,acetylcholine, norepinephrine and nitric oxide.

(ii) Inhibitory Neurotransmitters: These are exemplified byacetylcholine, norepinephrine, glycine, GABA, serotonin, and dopamine.

In this regard, it has been long recognized that some specificneurotransmitters can function in a dual capacity—i.e., these agents canact as both excitatory and inhibitory neurotransmitters. Acetylcholineand norepinephrine are vivid examples and instances of oneneurotransmitter exhibiting both such capacities and functions in-vivo.

B. In addition, the known kinds of neurotransmitter are often catalogedinto three categories of chemical composition, based on theirstereochemical structures. The usual three categories are the biogenicamine neurotransmitters; the peptide neurotransmitters; and the aminoacid neurotransmitters.

The Biogenic Amine Neurotransmitters

Biogenic amine neurotransmitters have been studied the longest and areprobably the best understood in terms of their relationship to humanpsychological disturbances. Among the predominant biogenic amineneurotransmitters which have been characterized are those summarilydescribed below:

Acetylcholine: It is synthesized in the presynaptic terminal from acetylcoenzyme A and choline in the presence of choline acetyltransferasesenzyme and is secreted by neurons in many areas of nervous system.Acetylcholine functions as both inhibitory and excitatory transmitter;but it is more known for its inhibitory action at some peripheralparasympathetic nerve endings—e.g., inhibition of heart by the vagusnerve. Acetylcholine is associated with muscle activation, learning, andmemory. Alzheimer's type dementia in particular has been directly linkedto acetylcholine function.

Norepinephrine: A substance which influences human sleep and alertnessand is believed to be correlated to the fight or flight stress response.It is secreted by the terminal neurons whose cell bodies are present inthe brain stem and hypothalamus. In particular, neurons secretingnorepinephrine located in the ‘locus ceruleus’ send nerve fibers towidespread areas of brain to help in controlling the overall activityand moods of mind such as increasing the level of wakefulness.

It also acts as inhibitory as well as excitatory transmitter. Mostpostganglionic neurons of the sympathetic nervous system also secreteit, where it excites some organs and inhibits others.

Epinephrine: A composition usually thought of as a stress hormonemanaged by the adrenal system, but which also acts as a neurotransmitterfor neurons in the human brain.

Noradrenaline: This is mainly an excitatory agent that induces physicaland mental arousal and elevated mood. Its in-vivo production is centeredin an area of the brain called the locus coreuleus, which is one ofseveral putative candidates for the brain's ‘pleasure’ centre.

Dopamine: A compound which is released by neurons that originate in thesubstania nigra, and acts in-vivo as an inhibitory transmitter. Itcontrols arousal levels in many parts of the brain and is vital forgiving physical motivation. When levels are severely depleted, as inParkinson's disease, people may find it impossible to move forwardvoluntarily. Low dopamine is also implicated in mental stasis; and thusLSD and other hallucinogenic drugs are believed to function via thedopamine system.

Glycine: It is released mainly at synapses in the spinal cord. It is theinhibitory transmitter.

Serotonin: The nuclei origination in the median raphe of the human brainstem secret serotonin. It acts to inhibit pain pathways in the cord andalso functions as an inhibitor of higher regions of nervous system(which is believed to help control the mood of the persons); and has aprofound effect on mood and anxiety—high levels of it, or sensitivity toit, are associated with serenity and optimism. Also, it has a role inmodulating anxiety, sleep, appetite and sexuality. Serotonin reuptakeinhibitors (SSRIs) are generally considered first line medications totreat panic disorder.

Nitric Oxide: It is secreted by nerve terminal present in those areas ofbrain which are responsible for long-term behavior and memory. Nitricoxide is synthesized instantly when needed. It changes the intracellularmetabolic functions that modify the neuronal excitability.

Histamine: In-vivo, histamine is thought to influence arousal, attentionand learning. It is also released in response to an allergic reaction.Antihistamines, which are commonly used to treat allergies, share thecommon side effects of sedation, weight gain and low blood pressure.

The Peptide Neurotransmitters

Peptide neurotransmitters are associated with mediation of theperception of pain, stimulation of the appetite, regulation of mood andother multiple functions. Abnormalities in peptide neurotransmittershave been associated with the development of schizophrenia, eatingdisorders, Huntington's disease and Alzheimer's disease.

Cholecystokinin (CCK): This peptide is a fairly new discovery that hasreceived a lot of attention in the last decade. CCK increases relaxationinducing GABA while decreasing dopamine. Reported studies have linkedCCK with anxiety and panic attacks in people with panic disorder.

Substance P: The study of neuropeptides actually began more than 60years ago with the accidental discovery of substance P, a powerfulhypotensive agent. The peculiar name derives from the fact that thismolecule was an unidentified component of powder extracts from brain andintestine.

Chemically, Substance P is an 11-amino-acid peptide, and is present inhigh concentrations in the human hippocampus, neocortex, andgastrointestinal tract; hence its historical classification as abrain/gut peptide. Substance P is also released from C fibers, thesmall-diameter afferents in peripheral nerves that convey informationabout pain and temperature (as well as postganglionic autonomicsignals).

Substance P is also a sensory neurotransmitter in the spinal cord, whereits release can be inhibited by opioid peptides released from spinalcord interneurons, and results in the suppression of pain. The diversityof Substance P is highlighted by the finding that the gene coding forsubstance P also encodes a number of other neuroactive peptides,including neurokinin A, neuropeptide K, and neuropeptide γ.

Opioids: These peptides are so named because they bind to the samepostsynaptic receptors activated by opium. The opioid peptides werediscovered in the 1970s during a search for endogenous compounds thatmimicked the actions of morphine. It was hoped that such compounds wouldbe analgesics, and that understanding them would shed light on drugaddiction.

The endogenous ligands of the opioid receptors have now been identifiedas a family of more than 20 opioid peptides that fall into threefamilies: the endorphins, the enkephalins, and the dynorphins. Eachmember of these families is liberated from an inactive pre-propeptidecompound (pre-proopiomelanocortin, pre-proenkephalin A, andpre-prodynorphin) derived from distinct genes. Opioid precursorprocessing in-vivo is carried out by tissue-specific processing enzymespackaged into vesicles along with the precursor peptide in the Golgiapparatus of the cells.

Opioid peptides are widely distributed throughout the human brain andare often co-localized with other small-molecule neurotransmitters (suchas GABA and 5-HT). In general, these peptides tend to be depressants.When injected intracerebrally, they act as analgesics and have beenshown to be involved in the mechanisms underlying acupuncture-inducedanalgesia. Opioids are also involved in complex behaviors such as sexualattraction and aggressive/submissive behaviors; and they have also beenimplicated in psychiatric disorders such as schizophrenia and autism,although the evidence for this is debated. Unfortunately, the repeatedadministration of opioids leads to tolerance and addiction

The Amino Acid Neurotransmitters

These compositions are viewed by some experts as the main players in theneurotransmission process. There are functionally two known kinds ofmajor amino acid neurotransmitters:

Gamma-aminobutyric acid (GABA): GABA is a major inhibitoryneurotransmitter that acts through a negative feedback system to blockthe transmission of a signal from one cell to another. It is importantfor balancing the excitation in the brain. The nerve terminals secreteit into the spinal cord, cerebellum, basal ganglia and into differentareas of the cortex; and once there, it causes inhibition of signal fromone cell to another. Benzodiazepines (anti-anxiety drugs) work on theGABA receptors of the brain, inducing a state of relaxation.

Glutamate and Aspartate: This is the human brain's major excitatoryneurotransmitter, and is vital for forging the links between neuronsthat are the basis of learning and long-term memory. Glutamate issecreted by presynaptic terminals in many of the sensory pathways whichenter the central nervous system as well as many areas of cerebralcortex. It functions as excitatory transmitter and is the most abundantchemical messenger in the brain.

It is important also to note that GABA and glutamate are carefullyorchestrated to balance each other. Dysfunction of one of these aminoacid neurotransmitters affects the function of the other. Some expertsbelieve that their excitatory and inhibitory balance influences allbrain cells.

C. It is well documented via the published medical literature thatseveral different neurotransmitters can be released from a single nerveterminal as co-transmitters; and these co-transmitters often includeneuropeptides and small molecule neurotransmitters. Thus, in addition toacting as neurotransmitters in their own right, neuropeptides can act asco-transmitters; and in their role of co-transmitters, they can activatespecific pre- or postsynaptic receptors to after the responsiveness ofthe neuronal membrane to the action of ‘classical’ neurotransmitters,such as noradrenaline and serotonin.

Moreover, it has been long known that three particularneurotransmitters—serotonin, noradrenaline and dopamine—are intimatelyinvolved in the day to day control of many of our mental states;sometimes acting alone, and at other times acting together. This featureof overlapping control via interactions of serotonin, noradrenaline anddopamine is illustrated by FIG. 1 herein.

These three particular neurotransmitters, as well as the many otherkinds of neurotransmitters known to date, play a pivotal role in thepathological basis of mental illness and diseases of the brain. Much ofthe evidence for this stems from the empirically proven fact that mostof the effective antidepressant drugs are thought to work by changingeither serotonin and/or noradrenaline metabolism, or by modifyingreceptor sensitivity to these neurotransmitters.

In-Vivo Neurotransmitter Imbalances

A. Neurotransmitter-related disorders occur when the current levels ofneurotransmitters are unable to properly relay the electrical signalfrom one nerve cell (neuron) to the next. A neurotransmitter imbalancecan result from the quantity levels being either too high or too low.

Clearly, neurotransmitters quantitatively exist in a delicate balancewith one another in-vivo. If the levels of one or more neurotransmittersbecome too low, the dynamic balance in-vivo can shift and otherneurotransmitter levels can become too high. Thus typically, if thequantitative levels of neurotransmitters are low, the nerves fireineffectively or not at all. In comparison, if the quantitative levelsof neurotransmitters are too high, the nerves of the CNS may fireinappropriately.

A substantial neurotransmitter imbalance can and will cause seriousmedical consequences. The recognized effects of substantialneurotransmitter imbalances in-vivo have been clinically linked to allof the following medical problems:

-   -   Attention issues (lack of focus and motivation, poor        concentration, and ADD);    -   Learning difficulties and development delays (young children);    -   Hyperactivity and ADHD for both children and adults;    -   Sleeping problems (fatigue, problems falling asleep, tossing and        turning, etc.);    -   Menopause related issues (hot flashes, mood swings, night        sweats);    -   PMS and mood changes from oral contraception (mood swings,        aggressiveness, irritability, sadness, lack of libido);    -   Weight issues and appetite control (cravings, overwhelming        hunger, etc.);    -   Depression (sadness, lack of motivation, mood swings, etc.);    -   Migraine headaches;    -   Anxiety (irritability, nervous, obsessive-compulsive,        insecurity, racing thoughts, restlessness);    -   Libido (lack of sex drive for women and men, orgasm issues,        erectile dysfunction, etc.

B. Of the many factors affecting neurotransmitter balance in-vivo, fourcauses stand out as the most prevalent. These four predominant factorsare: (i) chronic stress; (ii) poor diet; (iii) neurotoxins; and (iv)human genetics.

Chronic stress is typically the primary contributor to neurotransmitterimbalance in-vivo. Stress, both emotional and physical, can causeneurons to use up large amounts of neurotransmitters in order to helpthe person cope with his problems. Chronic daily stresses—varying from abusy career, to a stressed personal relationship, to a bacterial orviral infection—will tax the nervous system; and over time, depleteneurotransmitter quantities.

Poor dietary habits often lead to nervous system imbalances in-vivo,especially if the poor diet is combined with high stress. The body mustsynthesize the majority of its neurotransmitters from nutrients,primarily amino acids and proteins, which are obtained in the diet orthrough dietary supplements. However, diets with insufficient proteinsor too many high glycemic carbohydrates will increase excretion ofendogenous neurotransmitters. Also, diets low in Omega-3 fatty acidswill routinely lead to poor neuron function, because human brain cellmembranes are composed primarily of lipids and Omega-3 fats help tostabilize these membranes.

As concerns neurological toxins, there are a vast amount ofenvironmental toxins in the world we inhabit; not to mention the use ofalcohol, nicotine, and caffeine that also affect brain chemistry andnervous system health. The importance of toxin cleansing is importantfor every person, but especially for those individuals withneurotransmitter imbalances in-vivo.

The predisposition effect of personal genetics is also clearlyestablished. Some individuals are intrinsically metabolicallypredisposed to exhibit neurotransmitter deficiencies or excesses; andthese predispositions are directly attributable to one's own genetics.Also, certain kinds of health conditions, such as depression andattention deficit/hyperactivity disorder, are found to existconsistently in most if not all the members of a single family or asingle set of intimately related persons. For these persons,neurotransmitter deficiencies or excesses are effectively unavoidable.

The True Value of Cognitive Function Enhancement

Human cognition is often defined as the set of functional processes ahuman brain uses to receive, organize and retain information. Thesehuman cognitive brain functions typically include: acquiring information(perception); gathering and selecting (attention); representing andcomprehending (understanding); retaining and recalling information(memory); and using recollection to direct and guide behavior (reasoningand coordination of motor outputs).

Interventions to improve cognitive function may be directed at any oneof these core faculties; and any intervention that is aimed atcorrecting a specific pathology or defect of a cognitive subsystem maybe properly characterized as being therapeutic in effect.

Accordingly, a cognitive enhancement is an intervention that improvesbrain function in some way other than repairing cells and tissues orremedying a specific dysfunction. In meaningful use and effect,therefore, any distinction between a therapy and an enhancement is oftendifficult to discern, and functionally lacks practical significance. Forexample, cognitive enhancement for a person whose present natural memoryis poor might result in that person having an improved memory that isstill worse than that of another individual who retains a fairly goodmemory despite suffering from an identified pathology (such asearly-stage Alzheimer's disease). Cognitive enhancement is thus arelative term, with the point of reference always being the degree offunctional capability for a single identifiable human before and afterintervention.

A cognitively enhanced person, therefore, is not necessarily somebodywith particularly high (let alone above average) cognitive capacities.Instead, a cognitively enhanced person is someone who has benefited froman intervention that improves the performance of at least oneidentifiable cognitive function without necessarily correcting anexisting identifiable pathology or underlying cause for dysfunction ofthat cognitive ability.

The Spectrum of Cognitive Enhancement Formats

The conventionally available range of cognitive enhancement agentsinclude not only medical and pharmaceutical interventions as such; butalso encompass psychological interventions (such as learned mentalroutines or mental strategies), as well as improvements via externaltechnological and institutional structures that support cognition. Aparticularly distinguishing feature of all cognitive enhancementformats, however, is that they improve core cognitive capacities ratherthan merely concentrate upon narrowly defined skills or domain-specificknowledge.

Nevertheless, most efforts to enhance cognition today are of a rathermundane nature, and some of these techniques have been practiced forthousands of years. One prime example is education and training, wherethe intervention goal is often not only to impart specific skills orinformation, but also to improve general mental faculties such asconcentration, memory, and critical thinking. Other forms of mentaltraining, such as yoga, martial arts, meditation, and creativity coursesare also in common use for this purpose.

In the main, however, most persons today prefer to use one or morephysiologically active agents for cognitive enhancement.

Physiologically Active Agents Conventionally Used for Human CognitiveEnhancement

A wide range of very different physiologically active agents arecommonly employed today to enhance cognitive functions of the humanbrain; but, in general, many of these physiologically active agents arecollectively and cumulatively known to have poor efficacy in humans,with typically expected failure rates of about 50% [see for example,Turner E H, Matthews A M, Linardatos E, Tell R A, Rosenthal R. Selectivepublication of antidepressant trials and its influence on apparentefficacy, N. Engl J Med, 2008, 358: 252-260; and Rubinow D R, Treatmentstrategies after SSRI failure—good news and bad news, N Engl J Med,2006, 354:1305-1307].

It is noteworthy that a series of qualitatively different categories ofphysiologically active agents have been commonly used by humans eitherhabitually or at least occasionally for cognitive enhancement. Theseindividual categories include at a minimum: (1) highly potentpharmaceutical drugs and other pharmacologically active formulations;(2) the recreational illicit drugs; (3) stimulants and energy producingfoods and beverages; and (4) nootropic substances. Each of these fourindividual categories is briefly reviewed below.

1. Highly Potent Pharmaceutical Drugs and Other Pharmacologically ActiveFormulations

Constituting this first broad category are the compositionally definedand well characterized chemical classes of pharmaceutical drugs andother similar pharmacologically active formulations. Within this broadcategory, there are a range of very different and distinct classes ofdrugs.

By conventional medical definition, a drug is any one or more of thefollowing: (a) a substance used as a medication or in the preparation ofmedication; (b) according to the Food, Drug, and Cosmetic Act, is asubstance recognized in an official pharmacopoeia or formulary; (c) asubstance intended for use in the diagnosis, cure, mitigation,treatment, or prevention of disease; (d) a substance other than foodintended to affect the structure or function of the living body; and (e)a substance intended for use as a component of a medicine, but is not adevice or a component, part, or accessory of a device

Among the best known and most frequently employed of these drug chemicalclasses are those summarily described below. One specific class of suchchemically defined pharmaceutical drugs is the Selective SerotoninReuptake Inhibitors (hereinafter “SSRIs”), which typically include thosedrug formulations conventionally known today as “Prozac”, “Zoloft”,“Lexapro” and the like. However, this class of SSRI agent as a whole isonly marginally effective as therapeutic treatments to correctneurotransmitter deficiencies; and all of the known SSRI formulationsare prescription-only drugs, and thus have the added disadvantages ofbeing expensive in cost, being of very limited tolerance in humanbodies, and causing major systemic side effects [see for example: Hu XH, Bull S A, Hunkeler E M, et al., Incidence and duration of sideeffects and those rated as bothersome with selective serotonin reuptakeinhibitor treatment for depression: patient report versus physicianestimate, J Gin Psychiatry, 2004, 65: 959-965; Stone M B & Jones M L,Clinical review: relationship between antidepressant drugs and suicidalbehavior in adults”, Overview for December 13 Meeting ofPsychopharmacologic Drugs Advisory Committee (PDAC), FDA, pp. 11-74;Levenson M, Holland C., Statistical evaluation of suicide in adultstreated with antidepressants, Overview for December 13 Meeting ofPsychopharmacologic Drugs Advisory Committee (PDAC), FDA, pp. 75-140;Olfson M, Marcus S C, Shaffer D., Antidepressant drug therapy andsuicide in severely depressed children and adults: a case-control study,Archives of General Psychiatry, 2006, 63: 865-872; Clayton A H,Antidepressant-associated sexual dysfunction: a potentially avoidabletherapeutic challenge, Primary Psychiatry 2003, 10: 55-61; Kanaly K A,Berman J R., Sexual side effects of SSRI medications: potentialtreatment strategies for SSRI-induced female sexual dysfunction, CurrentWomen's Health Reports, 2002, 2: 409-416; and Fava M. Weight, gain andantidepressants, J Clin Psychiatry, 2000, 61(11): 37-41].

Benzodiazepines are another distinct chemical class of pharmacologicaldrugs; and are exemplified by the drugs “Valium”, “Xanax”, and“Librium”. All of these agents are prescription-only drugs; and are wellrecognized as producing an anxietolytic effect in-vivo, by acting on theGABA cell receptors. The GABA effects produced in-vivo by this class ofdrugs characteristically cause significant muscle relaxation and oftenmarkedly impair human cognitive functions [see for example: Ballenger JC., Benzodiazepine receptors agonists and antagonists, In Sadock V A,Sadock B J, Kaplan H I (eds.), Kaplan & Sadock's Comprehensive Textbookof Psychiatry (7th ed.), Lippincott Williams & Wilkins, 2000, pp.2317-23; Barker M J, Greenwood K M, Jackson M, Crowe S F, Cognitiveeffects of long-term benzodiazepine use: a meta-analysis”, CNS Drugs,2004, 18: 37-48; Stewart S A., The effects of benzodiazepines oncognition, J Clin Psychiatry, 2005, 66: 9-13; Nelson, T, McSpadden M,Fromme K, Marlatt G, Effects of alcohol intoxication on metamemory andon retrieval from long-term memory, J Experimental Psychology, 1986,115; 247-254; Ginzburg R, Skeletal muscle relaxants, Pharmacotherapy,2008, 28:207-13].

A third chemical class of well characterized pharmacologically activedrugs are the Monoamine Oxidase Inhibitors (hereinafter “MAOs”). MOAsare active compositions which act in-vivo to block the MAO enzyme,thereby delaying the in-vivo metabolism of dopamine, serotinin, andnorepinephrine at the cell receptor level. However, MOA agents areseverely limited in clinical usage owing to their causing significantside effects in humans, such as hypertension and mania [see for example:Marley E, Blackwell B, Interactions of monoamine oxidase inhibitors,amines, and foodstuffs, Adv Pharmacol Chemother, 1970, 8:185-239; andShopsin B & Kline N S, Monoamine oxidase inhibitors: potential for drugabuse, Biol Psychiatry, 1976, 11:451-456].

2. Recreational Illicit Drugs

In the second general category of commonly used active agents, therecreational illicit drugs have frequently been used by humans to causemajor changes of mental state and mood enhancement. This category ofactive agents is exemplified by the large number of different opiatesand amphetamines commonly known and illicitly sold today, all of whichlead seem invariably to cause addiction in some degree in humans. Amongthe most commonly known of these are the following.

Amphetamine-type stimulants (such as Adderall, Dexedrine, Desoxyn, etc.)are Schedule II controlled substances in the United States, and Class Bdrugs in the United Kingdom, with comparable legal controls in effect inmost countries throughout the world. They are prescribed forattention-deficit disorders, narcolepsy, and certain cases of obesity;and are issued to counteract fatigue and to enhance performance forpilots in the armed forces of the United States of America. These alsoheighten alertness, mental focus, vigilance, stamina, and sex drive.They tend to be habit-forming, and exhibit side effects with prolongedor heavy use. Personal importation of amphetamine-class drugs isprohibited in many countries, and their use for recreation or forperformance enhancement without a medical prescription is likewiseillegal in most countries.

LSD, a psychedelic drug. When administered at higher doses, humansensory effects seem qualitatively different. Many psychedelic drugs arepurported to produce this overwhelming effect on the mind. This effecton the creative process is a phenomenon that may be due to ascendingtraffic in the reticular activation system, which can result in stimulusoverload. LSD produces hallucinogenic and entheogenic effects at dosesas low as 30-40 μg (micrograms); and may also cause cognitive shifts, aswell as synesthesia. LSD sometimes spurs long-term or even permanentchanges in a user's personality and life perspective.

Others examples include 4-methylaminorex; Pemoline (Cylert); Psilocybinand Psilocin; MDPV; Mescaline; and 2C-D.

3. Stimulants and Energy-Producing Foods and Beverages

As the third general category of physiologically active agents, therepresently exist a surprisingly large variety of alternatively formulatedstimulants and energy-producing foods and beverages all of which haveattempted (at least in part) to address the human need for mood changesand cognitive enhancement.

A. One major family of such active agents is stimulants. Stimulantsenhance human memory by increasing neuronal activation or by releasingneuromodulators, thereby facilitating the synaptic changes that underlielearning. Thus, the earliest known enhancer drugs were mainlynonspecific stimulants and nutrients. In antiquity for example, honeywater (hydromel) was used for doping purposes.

Similarly today, nicotine is a stimulate known for its complexinteraction with attention and memory occurs; and strychnine is known tobe a stimulant which facilitates learning. It is especially noteworthytherefore to recognize that both nicotine and strychnine exist inmeaningful quantities in commercially sold tobacco products such ascigarettes, cigars, and pipe mixtures.

Among the more commonly known and used stimulants are: Adrafinil;Caffeine; Coffee; Nicergoline; Nicotine; Methylphenidate (Ritalin);Cocaine; Dextroamphetamine (Adderall, Dexedrine); Modafinil (Provigil);Phenibut; Theophylline; Amphetamines; and Carphedon (Phenotropil).

In addition, attention is directed to the fact that a huge majority ofcommercially available products exemplifying and representing thisfamily of formulations use the stimulant caffeine as their primaryactive ingredient. The reports in the published scientific literaturehave revealed that caffeine metabolites (such as paraxanthine,theobromide, and theophylline) will cross the blood-brain barrierin-vivo to cause reversible blockade of adenosine receptors in thebrain; and via such blockade of adenosine receptors create asimultaneous increase for epinephrine and/or norepinephrine—which thenserves as the chemical means to inhibit the need for sleep and toaugment mood, alertness, and attention span in the human mind.

However, among the major drawbacks of such stimulants are: They arerestricted in effect and quantitative usage by severe limitations ofhuman tolerance; and they are restrained in their efficacy to produce adesirable positive mental state in humans, such as euphoria andpleasurable affective stimulation [see for example: Daly J W, Fredholm BB, Caffeine-an atypical drug of dependence, Drug Alcohol Depend, 1998,51: 199-206; and Tunnicliffe J M, Erdman K A, Reimer R A, Lun V, ShearerJ, Consumption of dietary caffeine and coffee in physically activepopulations: physiological interactions, Appl Physiol Nutr Metab, 2008,33:1301-1310].

B. A second distinct family of active agents within this category is theenergy-producing foods and beverages. It has been long recognized thatboth changes of food eating habits and dietary supplements can affecthuman cognition. For example: In order to maintain optimal functioningability, the human brain requires a continuous supply of glucose, itsmajor energy source. Increases in glucose availability, from theingestion of natural sugars in food or via the supplemented presence ofthe acute stress hormone norepinephrine, improve human memory—with theresulting cognitive enhancement effects being particularly pronounced inhighly demanding mental tasks [see for example: Nybo L, Pedersen K,Christensen B, Aagaard P, Brandt N, Kiens B, Impact of carbohydratesupplementation during endurance training on glycogen storage andperformance, Acta Physiol, 2009, 197:117-127].

In a similar fashion, creatine—a nutrient that improves energyavailability in the body—appears to benefit overall cognitiveperformance and reduce mental fatigue for many persons. In addition,besides being an energy-producing source, food fit for human consumptioncan contribute to human cognition by providing those particular aminoacids needed for the in-vivo production of synapse neurotransmitters;and this need is particularly critical during periods of continuingmental stress or of sustained concentration. There is also ampleevidence that micronutrient supplementation increases non-verbalintelligence for some children [see for example: Ratarness N A, HoffmanJ R, Ross R, Shanklin M, Faigenbaum A D, Kang J., Effects of an aminoacid/creatine energy supplement on the acute hormonal response toresistance exercise, Int J Sport Nutr Exerc Metab, 2007, 17:608-623;Bemben M G & Lamont H S, Creatine supplementation and exerciseperformance: recent findings, Sports Medicine, 2005, 35:107-25; KreiderR B, Effects of creatine supplementation on performance and trainingadaptations, Molecular and Cellular Biochemistry, 2003, 244:89-94; EliaJ, Ambrosini P J, Rapoport J L, Treatment ofattention-deficit-hyperactivity disorder, N Engl J Med, 1999,340:780-788; Eilander et al, Multiple micronutrient supplementation forimproving cognitive performance in children: systematic review ofrandomized controlled trials, Am J Clin Nutr, January 2010, 91:115-130].

Merely to illustrate the range and variety of energy-producing foods andbeverages, many routinely consumed food items are rich sources ofsubstances with ostensible benefits. These include:

(i) Nuts, in particular walnuts are rich sources of alpha-linolenic acid(ALA), a type of omega-3 fatty acid.

(ii) Oily fish, such as salmon or fresh tuna are good sources of omega-3fatty acids such as eicosapentaenoic acid and docosahexaenoic acid; andwhose lack in diet has been associated with increased risk of mentalillnesses such as depression, anxiety, aggressive behavior,schizophrenia, or hyperactivity in children.

(iii) Berries which contain high amounts of anthocyanins have beneficialeffects. Blueberries, blackberries and raspberries are among thosehaving the highest anthocyanin content; and these act to provide acombination of neuroprotective and neurogenesis effects.

4. Nootropic Agents

The term “Nootropic” was first coined in 1972, and is a broad titleformed from the Greek words nous (mind) and trepein (to bend).Nootropics as a whole are a diverse category of agents which encompassmany different compositions and formats; and often are identified byalternative names such as ‘cognitive enhancers’, ‘smart supplements’,‘intelligence boosters’, ‘memory enhancers’, and the like. Thus,nootropics are a very broad category of physiologically activesubstances which are individually capable of enhancing cognition,memory, and increasing the long term health of the brain.

Many nootropic agents have an in-vivo effect of mimicking the action ofsynapse neurotransmitters in the brain (such as acetylcholine,serotonin. dopamine and glutamate). However, the manner in which theyact and the mechanisms of action in-vivo by which they achieve theseresults is quite different in each instance.

Notably, some nootropic agents work by increasing the quantity of nervegrowth factor and cause new nerve cell growth in the brain; othernootropic agents work by increasing the oxygen supply of the brain(i.e., they are brain specific vasodilators); still others function asshort term stimulants which cause a cognitive enhancing effect when usedsparingly, in very small quantities.

Requisite Criteria for Qualification as a Nootropic Agent

For a substance to be properly classed as a ‘nootropic agent’, it mustmeet and satisfy certain physiological activity criteria, which includethe following:

1. A nootropic substance should increase or improve at least onerecognized cognitive brain function, such as: acquiring information(perception); gathering and selecting (attention); representing andcomprehending (understanding); retaining and recalling information(memory); and using recollection to direct and guide behavior (reasoningand coordination of motor outputs).

2. A nootropic substance should protect against consequences that whichcan disturb or disrupt the human mental state and avoid causing changesin overt human behavior—e.g., causing hypoxia (low oxygen levels in thebrain);

3. A nootropic substance should always protect the human brain from therisks of causing either chemical or physical injury to the nerve cellsand neural tissues;

4. A nootropic substance should improve or increase the in-vivoefficiency of subcortical mechanisms and should the facilitation ofinterhemispheric flow of information;

5. A nootropic substance should demonstrate an absence of negativepharmacologic effects typical of psychotropic drugs;

6. A nootropic substance should initiate very few side effects andexhibit virtually no toxicity in-vivo.

Nootropic Families and Membership

As merely representative and illustrative of the most commonly usednootropic agents today, a short listing of specific subset families andtheir constituent members is provided below.

The Family Membership of Racetams

The family membership of Racetams typically include the four chemicalanalog compositions of Piracetam, Aniracetarn, Oxiracetarn, andPrarniracetann. The four main commercially available “racetam”nootropics all share a pyrrolidone nucleus, whose stereochemicalstructure is shown below,

while Piracetam, Oxiracetarn, and Pramiracetam also include and commonlyshare an acetyl group.

A. Chronologically, Piracetam was the first to be discovered (1964); andthe term ‘nootropic’ was created to identify and distinguish its affectsfrom other types of compositions. Piracetam (and its analogs) is a watersoluble compound; and is a slight positive allosteric modulator of theAMPA receptor (i.e., Piracetam binds to the allosteric site on the AMPAreceptor and may increase its functioning). Researchers are stillunclear today as to Piracetam's exact mechanism of action in-vivo, butit is believed to act on ion channels in the brain leading to a generalincrease in synaptic transmission and excitability rather than directlyacting as a neurotransmitter agonist.

Aniracetarn was discovered in the 1970's; and is a fat soluble analogueof Piracetam. It's about 2×-5× stronger in effect than Piracetam on agram for gram basis. Aniracetarn is known to be a modulator of the AMPAreceptor which is involved in fast synaptic transmission in the brain.Many users have reported Aniracetarn to be anxiolytic (anxiety reducingin humans).

Oxiracetarn is water soluble analogue discovered some time afterPiracetam. It is believed to be around 5×-8× more powerful thanPiracetam on a gram for gram basis. Many users of Oxiracetarn report afast onset of enhancement effects, sometimes within a few hours time.Other users of Oxiracetarn commonly report a slight stimulant effectrather than an anxiolytic effect (like Aniracetarn).

Pramiracetam is generally considered to be the most potent of theRacetams. Discovered in the late 1970's, Pramiracetam (also sometimescalled ‘Pram’ or ‘Prami’) is a fat soluble analog of Piracetam. On agram for gram basis, Pramiracetam is around 5×-10× stronger thanPiracetam. Some human users of Pramiracetam report having an enhancedfocus and a greater clarity of thought. For others, however,Pramiracetam can be far too intense.

B. Note also that the Racetams as a single family of member compounds(especially Piracetam and Oxiracetarn) are closely related in formulaand structure to the amino acid Pyroglutamic Acid. Pyroglutamic Aciditself is a discrete composition which has been shown in some studies tohave weak nootropic activity. Pyroglutamic Acid is naturally present inmany human foods, as well as the mammalian brain.

Each of the Racetarn analogs constituting this particular family ofnootropic agents provide in-vivo benefits for humans by inducing bettermemory retention, better memory recall, and increased acetylcholineturnover. Individual human reactions and in-vivo responses to the use ofsuch racetams varies considerably with the individual.

The Family Membership of Choline Supplements

Choline is an essential nutrient needed for health promotion and diseaseprevention in individuals of all ages. It is essential for many oflife's most basic functions including the normal functioning of all ofthe body's cells, brain and nerve function, liver metabolism and thetransportation of nutrients throughout the body.

Acetylcholine (Ach) is a specific synapse neurotransmitter compoundwhich is vital for learning, memory and concentration. An increasedtransmission of Acetylcholine in the synapse of nerve cells (neurons)demonstrably facilitates human memory, concentration, focus, andhigh-order thought processes (such as abstract thought, mentalcalculation, innovation, etc.). Acetylcholine synapse transmissionin-vivo is also conventionally known as ‘cholinergic’ transmission,because Choline is a required component in and thus is vital for thein-vivo synthesis of the bioactive neurotransmitter Acetylcholine.

Cholinergics are, by common medical definition, substances that affectthe neurotransmitter acetylcholine, or the components of the humannervous system that use or rely upon acetylcholine. In the reportedscientific literature, numerous studies have shown that the purposefulextraneous introduction of various Choline supplements serve to supportthe normal functions of the human brain.

Thus, it is recognized that increasing the in-vivo availability of theneurotransmitter Acetylcholine within the brain cavity may sometimesimprove neural functions and increase the duration of mental alertnessand concentration. Nevertheless, it is also well documented andrecognized in the published medical literature that markedlyoversupplying the human brain with extraneous Acetylcholine will cause adirectly opposite effect in-vivo—i.e., the in-vivo oversupply ofAcetylcholine will markedly reduce, rather than improve or increase,human cognitive functions and performance.

A diverse range of Choline supplements is conventionally known andcommonly available. Among the better known types and kinds of Cholinesupplements which are today commercially sold are the following.

(i) Choline precursors of acetylcholine. These typically include:Alpha-GPC (L-alpha glycerylphosphorylcholine); Choline alfoscerate;Citicoline; Choline bitartrate; and Choline citrate.

(ii) Cerebral Vasodilators. These typically include: Gingko Biloba andVinpocetine.

(iii) Nerve Growth Stimulators. These typically include: AcetylL-Carnitine (ALCAR); and Lion's Mane mushroom.

The Family Membership of Dopaminergics

A. Dopaminergics are a family of bioactive substances that affect thesynapse neurotransmitter Dopamine or the components of the nervoussystem that use Dopamine (DOPA) as a neurotransmitter.

Notably, Dopamine (whose chemical formula is C₆H₃(OH)₂—CH₂—CH₂—NH₂) is amember of the catecholamine chemical family; and is a natural forerunnerto and precursor compound for the synthesis of epinephrine (adrenaline)and norepinephrine (noradrenaline) in the human body. Dopamine itself asa distinct chemical composition is synthesized in-vivo via thedecarboxylation of L-DOPA by aromatic-L-amino-acid cecarboxylase.

Dopamine is a naturally existing neurotransmitter precursor used in-vivoto activate specific (dopamine) receptors present upon certain kinds ofneurons in the brain tissues. The hypothalamus also synthesizes andreleases it as a neurohormone, with its main function then being theinhibition of prolactin release from the anterior pituitary lobe.

In its role as a natural neurotransmitter precursor, Dopamine has a widevariety of applications in the brain. In particular, dopamine markedlyaffects the way the brain controls human movement; and a continuingshortage of dopamine in-vivo ultimately results in Parkinson's disease.Moreover, dopamine controls the flow of information to the frontal lobefrom other parts of the brain.

Disorders in dopamine levels of the brain cause declines inneurocognitive functions like memory, attention, and problem-solving.Clinically, an increase of dopamine can frequently improve the symptomsof people suffering from Parkinson's disease and other relatedneurological disorders. However, dopamine as a whole molecule cannotitself cross the blood-brain barrier in-vivo; and consequently,injecting or orally ingesting DOPA does not allow for its travel intothe brain. Instead, synthetic L-DOPA, which is a precursor to dopaminethat does in fact cross the blood-brain barrier, is often used. L-DOPAis able to cross the blood-brain barrier; and after entering the humanbrain tissues, is there chemically altered and converted into thebioactive entity dopamine.

B. It is critical to recognize what is Dopamine's long established rolein affecting human pleasure and motivation. Dopamine is markedlyassociated with the pleasure system of the human brain; and itscontinued presence in-vivo not only provides feelings of enjoyment, butalso reinforces those human behavioral activities which generate thosefeelings. Thus, ingestion of desired foods, overt sexual activity, andsimilar self-rewarding human behaviors and social experiences cause anadded release of Dopamine in-vivo; and neutral stimuli associated withintense pleasure (such as indulging in sexual fantasies or fetishes) andthe self-administration of certain recreational drugs also initiatedopamine synthesis and release in-vivo.

By common knowledge, the family membership of the Dopaminergicnootropics encompasses and includes all the conventionally knownprecursor compounds which can be employed to synthesize the bioactivedopamine molecule. Merely exemplifying this membership are the followingrepresentative substances: Mucuna pruriens (a seed powder); Tyrosine (aprecursor); Phenylalanine (a precursor); Levodopa (L-dopa); Yohimbe (atype of tree bark); Selegiline (L-depreny); Tolcapone (an inhibitor ofCOMT); and Theanine (an extracted ingredient of tea).

The Family of Serotonergics

Serotonergics are substances that specifically affect the synapseneurotransmitter serotonin or the components of the nervous system thatuse serotonin as a bioactive molecule in-vivo.

Serotonin is known to control human mood, sleep and appetite; and isproduced naturally within the human body by exposure to the rays of thesun. Also, certain foods are naturally high in serotonergics that makeyou sleepy or that make you feel good after eating them. For instance,turkey contains very large quantities of the serotonin precursorL-Tryptophan.

By definition therefore, the family membership of NootropicSerotonergics encompass and include all Serotonin precursors as well asthe true bioactive molecular entity 5-HTP.

Among the better known and conventionally available serotonergics arethe following: Griffonia simplicifolia; and Tryptophan (a precursorcompound).

Other Diverse Family Varieties

As exemplary of these highly diverse nootropic member substances, arepresentative and listing typically encompasses and includes all of thefollowing: Ashwagandha (Withania somnifera), a root also known as Indianginseng; Inositol, a sugar; Kava kava, a root; Lemon balm (Melissaofficinalis), a herb; Passion Flower; Rhodiola Rosea, a herb; St John'sWort, a herb; Siberian Ginseng (Eleutherococcus senticosus), a root;Sutherlandia frutescens, a herb; Theanine, an amino acid found in tea;Tianeptine, an anxiolytic anti-depressant; Vasopressin, a hormone;Niacin, a vitamin; Picamilon (also known as nicotinoyl-GABAnn,Pycamilon, or Pikamilon), a dietary supplement formed by combiningNiacin with GABA; and Grape Seed (Vitis vinifera).

SUMMARY OF THE INVENTION

The present invention as a whole encompasses and includes anon-prescription blended formulation suitable for oral ingestion by aliving human subject, and which after ingestion is able to induce a morepositive mood for and to initiate an observable enhancement of cognitivefunctions in a living human subject.

One aspect of the invention provides a minimalist blended formulationcomprising:

a controlled admixture of five types of essential active ingredients,each of which is able to cross the blood-brain barrier in-vivo, whereinsaid controlled admixture of essential active ingredients is limited to

(a) not less than two different naturally existing nootropic dopamineneurotransmitter agonists, each of which is present in an individualquantity ranging from about 10 mg/L to about 3000 mg/L,

(b) not less than one naturally existing nootropic acetylecholineneurotransmitter agonist which is present in an individual quantityranging from about 10 mg/L to about 1500 mg/L,

(c) not less than one naturally existing nootropic serotoninneurotransmitter agonist which is present in an individual quantityranging from about 10 mg/L to about 1600 mg/L,

(d) not less than one naturally existing nootropic gamma-aminobutyricacid neurotransmitter agonist which is present in an individual quantityranging from about 10 mg/L to about 5000 mg/L, and

(e) not less than one nootropic adenosine antagonist which is present inan individual quantity ranging from about 10 mg/L to about 1000 mg/L,

wherein the neurotransmitter replenishment balance factor for theadmixture of essential active agents mathematically is zero (“0”) invalue.

A second aspect of the invention also provides a non-prescriptionblended formulation suitable for oral ingestion by a living humansubject, and which after ingestion is able to induce a more positivemood for and to initiate an observable enhancement of cognitivefunctions in a living human subject.

This second aspect of the invention provides a maximal blendedformulation comprising:

a controlled admixture of five types of essential active ingredients,each of which is able to cross the blood-brain barrier in-vivo, whereinsaid controlled admixture of essential active ingredients is limited to

(a) not more than six different naturally existing nootropic dopamineneurotransmitter agonists, each of which is present in an individualquantity ranging from about 10 mg/L to about 3000 mg/L,

(b) not more than four different naturally existing nootropicacetylecholine neurotransmitter agonist, each of which is present in anindividual quantity ranging from about 10 mg/L to about 1500 mg/L,

(c) not more than three different naturally existing nootropic serotoninneurotransmitter agonist, each of which is present in an individualquantity ranging from about 10 mg/L to about 1600 mg/L,

(d) not more than three different naturally existing nootropicgamma-aminobutyric acid neurotransmitter agonist which is present in anindividual quantity ranging from about 10 mg/L to about 5000 mg/L, and

(e) not more than three different nootropic adenosine antagonist whichis present in an individual quantity ranging from about 10 mg/L to about1000 mg/L,

wherein the neurotransmitter replenishment balance factor for theadmixture of essential active agents mathematically is zero (“0”) invalue.

BRIEF DESCRIPTION OF THE DRAWING

The present invention can be more easily understood and betterappreciated when taken in conjunction with the accompany Drawing, inwhich

FIG. 1 is a graphic representation of the conventionally knownoverlapping inter-relationships for the three naturally occurringneurotransmitters dopamine, acetylcholine and serotonin.

DETAILED DESCRIPTION OF THE INVENTION

Depression and depressed mood negatively affect human cognitiveperformance. Feelings of sadness, guilt, helplessness, hopelessness,anxiety, and fear caused by depression detract from productive thought;while apathy, being a lack of motivation, drives and affects human moodssuch as curiosity, interest, and determination. Other indications andsymptoms which reflect human mood and influence human cognitiveperformance include disturbed sleep patterns, mental fatigue and loss ofenergy, trouble concentrating or making decisions; as well as ageneralized slowing and obtunding of cognition, including memory.Clearly then, modifying human mood causes marked improvements inintelligence and mental performance.

Mood disorders are believed to afflict 60% of the world population andto be related to neurotransmitter function which can be variableaccording to age, dietary deficiencies, heredity, environmental stress,and hormonal imbalances. Neurotransmitter dysfunction is thusmultifactorial, but typically includes several mechanisms including:insufficient production, deactivation by enzymes at the receptor level,an imbalance of neurotransmitters, poor reabsorption or uptake, andimproper synchronization and timing between neurotransmitter release andreceptor uptake.

For these reasons, the present invention relies upon and utilizes anentirely new concept of human mood enhancement via the concept of “anintegrated neuromodulation system”. In this unique approach and concept,five different classes of ‘neuromodulatory’ brain neurotransmitters (allof which are naturally existing the central nervous system) aresuccessfully integrated and employed collectively to produce positivemood enhancement for the individual person.

Via such integrated neuromodulation, the invention takes advantage ofthe fact that one particular kind of neuron can use multiple differentneurotransmitters concurrently to connect to and activate several otherneurons in the same anatomic locale. Such alternative neuromodulatorytransmitter agents are typically synthesized and released by a smallselect group of neurons dispersed in-vivo over large anatomic areas ofthe central nervous system. Each of these select neurons has an effectupon multiple adjacently located neurons; and consequently these selectneurons have the unique capability of activating many other neuronsconcurrently and collectively.

These select neurotransmitter systems are thus sets of select neurons inthe brain, which are able to express activity effects in large volumesof the brain, or in volume transmission. This select neuron capabilityand event stands in marked difference and contrast to the more usualsingle direct electrical synaptic transmission, in which one presynapticneuron directly influences a postsynaptic partner, such as a singleneuron reaching to one other neuron.

The “Integrated Neuromodulation” Effects Initiated by the Invention

In view of the foregoing, the present invention intentionally accessesand employs five discrete and naturally existing neurotransmittersystems in combination for implementing “integrated neuromodulation”in-vivo; and these are: the dopamine, serotonin, acetylcholine, gammaamino butyric acid, and adenosine systems. In order to recognize andappreciate properly what are the beneficial effects of implementing suchan “integrated neuromodulation”, the following points of information aredeemed to be particularly valuable.

(1) Neurotransmitter agents are deemed to be either excitatory orinhibitory in their actions, and exert their in-vivo activity throughreceptor sites at the synapse of the receiving neuron. In the presentinvention, the targeted excitatory neurotransmitter systems specificallyare the dopamine receptors and adenosine receptor blockade; while thetargeted inhibitory neurotransmitter systems specifically areacetylcholine, serotonin, and gamma aminobutyric acid receptors.

(2) Volume transmission is the process of activation of neurotransmittersystems on large portions of the brain. The volume transmission conceptis based on empiric evidence that the brain attempts to compensate fordeficiencies in neurotransmitter systems; but that the end physiologicresult is not precise, leading to compensatory stimulatory or inhibitoryactivity. Furthermore, neurotransmitter systems are interrelated, withmultiple regulatory functions. This concept will become evident in theneuromodulary hypothesis, the centerpiece of this invention, as thecentral role in mood enhancement.

(3) Dopamine is the major stimulatory neurotransmitter of the brain andis 3 to 4 times more abundant when compared to acetylcholineneurotransmitter, which is inhibitory. However, the number of dopamineneurons in the brain is limited, and is estimated at only about 30,000to 40,000 in total, with a loss of 13% per decade of life.

Also, dopamine is receptor site specific. For instance, dopamineproduced in the caudate nucleus facilitates posture, whereas dopamine inthe nucleus accumbens of the frontal cortex is associated with rapidityof movements and pleasure. These areas connect with the substantia nigraof the midbrain, which produces 80% of all dopamine in the brain.

As to its effects, dopamine produces feelings of psychological energyand sexual arousal, with diminished appetite and need for sleep.Addicting drugs (such as cocaine and amphetamines) produce a dopamineexcess, which can lead to permanent neuronal death and the consequenceof losing the capability for normal human pleasure responses.Furthermore, Parkinson's disease is the clinical result of degenerationof the substantia nigra of the brain—thereby resulting in dopaminedeficiency, and a loss of muscle coordination and both cognitive andaffective decline.

(4) Serotonin is an inhibitory neurotransmitter agent which has itsgreatest concentration in the pineal gland of the brain. Serotonin is animportant mood stabilizer in-vivo; and acts to decrease painsensitivity, aggressive behaviors, and libido (while also oftenproducing weight gain).

Clinically diagnosed depression afflicts 3 to 4% of the population; andis believed to be a result, at least in part, of serotonin deficiency.Noteably, the prevalent medical practice of administering selectiveserotonin reuptake inhibitors (SSRIs) markedly inhibit the reuptake ofserotonin neurotransmitter from the synaptic gap, thereby resulting inan increase in serotonin neurotransmitter action in-vivo.

(5) Acetylcholine is an inhibitory neurotransmitter agent withrelatively few receptors in the brain (and located in theinterpeduncular nucleaus near the substantia nigra of the midbrain); andwhere a majority of receptors are found outside the brain in theskeletal and smooth muscles controlled by the autonomic nervous system.

Acetylcholine produces REM sleep and is also important in memoryretention. Clinically, Alzheimer's disease is caused by a loss of cellsin the basal forebrain that secrete acetylcholine, resulting in memoryloss as well as a diminution of sensory and associative information forprocessing and motor activities.

(6) Gamma amino butyric acid (“GABA”) is the major inhibitoryneurotransmitter of the brain which is present in 30 to 40% of all brainsynapses, and highly concentrated in the substantia nigra of themidbrain, basal ganglia, hypothalamus, and hippocampus. GABAconcentrations in the brain are estimated to be 200 to 1000 times thatof either dopamine or acetylcholine.

In vivo, GABA produces smooth muscle relaxation; and can counteract themuscle hyperactivity associated with dopaminergic stimulation. Anxietyis the most prevalent worldwide psychiatric disorder, affecting 10 to30% of people; and GABAergic agents—such as alcohol, barbiturates, andbenzodiazepines—are very prevalent for recreational use.

(7) Adenosine receptors are present in high levels in the centralnervous system of the body. Activation of Adenosine receptors in thebrain slow metabolic activity and also affect the sleep-wake cycle.

A blockade of Adenosine receptors produces the reverse effect—i.e.,warding off drowsiness and restoring alertness—in addition to initiatingother stimulatory effects, such as faster and clearer flow of though,increased focus, and improved body coordination. Stimulatory effects onthe peripheral nervous system include muscle tremor and twitching.

(8) The present invention notably relies upon the use of nootropicagents as the active ingredients for implementing “integratedneuromodulation” in-vivo. Nootropic agents can produce an immense rangeof effects on human mental functions, including but not limited to:cognition, memory, intelligence, motivation, attention, andconcentration. These nootropic agents can work by a number of mechanismsincluding neurotransmitter replenishment, enzyme expression, and/orhormonal function, brain vascularity, and nerve growth. Moreover, manyof these nootropic agents can cross the blood-brain barrier in order toproduce psychoactive effects; and it is precisely for this reason thatin the present invention, only naturally occurring nootropic agents areused to implement “integrated neuromodulation” for five discreteneurotransmitter systems.

I. THE BLENDED FORMULATIONS OF THE INVENTION AS A WHOLE

It is noteworthy that the full range and variety of blended formulationsconstituting the present invention can be used by any living humansubject (but preferably by adults rather than children) to achieve thedesired effect of markedly modifying the attitudes, perceptions, andobserved social behaviors for such persons. In particular, the purposelyblended formulations can and will perform three related, but distinct,function in-vivo, which are:

(α) Cause a series of distinct biochemical changes in-vivo; which inturn will

(β) Initiate psychological consequences in that person; and which inturn will

(γ) Induce an observable increase in cognitive functions for that livinghuman subject.

Each of these is described in meaningful detail below.

(α). The present invention uses a balanced neurotransmitterneuromodulatory effect to produce a clinically significant effect inhumans. This is empirically demonstrated herein via human clinicalstudies which use a combination of low doses of five individual types ofnootropic neurotransmitter agents as a blended formulation which causesa series of distinct biochemical changes in-vivo. The orally ingestibleblended formulation is always a prepared admixture of five alternativeclasses of nootropic agents in low dose amounts which are neuroselectiveand will cross the human blood-brain barrier to produce concurrentstimulation of dopamine, serotonin, GABA, and acetylcholine receptors,with simultaneous reversible adenosine receptor blockade; which resultin a clinically significant ‘balanced neurotransmitter volumetransmission’.

This balanced neuromodulation of neurotransmitter systems produces adesirable mood enhancement state of temporary euphoria and pleasure inthe human without depleting other kinds or sources ofneurotransmitters—a severe limiting side effect and major drawback ofcurrent practices which use conventional pharmacologic agents, energydrinks, and recreational drugs. The blended formulations administered inlow dose amounts also are believed to have a protective effect at thebrain neurotransmitter receptor level and will produce the optimum levelof physiologic effect, while minimizing undesirable side effects andsystemic effects in the body. Also, because the blending of fivedifferent classes of nootropic agents are naturally existing foodelements which the body needs to produce the optimum level ofneurotransmitter supply, whatever the human body does not need or use,it will eliminate.

(β). The psychological events initiated within the person will generatea positive change in one's personal perceptions; evoke optimism as thesubjective state of mind; and elicit a more sociable attitude andfavorable mood as the observable behavior of the affected human person.

This more positive mental state of and better mood for the person standsin stark contrast and difference to the usual anxiety and mental anguishusually experienced by that person when confronted with mental tasks ofany consequence; is a significant betterment of the person's typicalpeace of mind and mental comfort; constitutes a meaningful reduction ofthe person's phobias, apprehensions, and fears (whether justified ornot); and results in a more favorable and gentler pattern of observedsocial behaviors.

Furthermore, it should be recognized also that, once the person hasexperienced such an increase in positive mood and enjoyed a truereduction of his existing apprehensions and fears; that individual willretain the memory of having had a more pleasant mental state of mind, aswell as having felt more at ease with himself and the world at large.This personal memory and recollection of a pleasant and more positiveexperience will typically cause that individual to reconsider the needor worth of his prior negative feelings, and encourage that person torecreate and regenerate for himself a more favorable mood and positivemental state again and again—as a protection for and safeguard againstthe next possible occurrence of anxiety, apprehensions, and fears.

Certainly for those persons who are frequently apprehensive or oftenuneasy in their minds, the value and benefit of having a prepared inadvance, oral ingestable blended supplement which can overcome one'sanxieties and overtly increase the motivation of and positive propensityfor the individual to grapple with controlling his own mental state—isboth a comfort and a relief—to the degree that the individual becomesmildly comfortable, if not enthusiastic, about his mental attitudes andthought processes. In contrast, even for those blessed persons whosetypical attitude and state of mind is merely neutral or trulydispassionate in their moods, such persons will have the benefit anddistinct advantage that an orally ingestible blended supplement isavailable as a temporary stop-gap measure should they find themselves inunusually difficult or overwhelming life circumstances.

(γ). In addition to the initiation of a more positive state of mind, theother major result and effect of ingesting the blended supplement is anobservable amplification of human brain functions and a measurableincrease of human concentration, focus and memory. Thus, the blendedsupplement can and will induce an observable and objectivelydeterminable enhancement of cognitive functions in the individual—i.e.,improve the functional processes a human brain uses to receive, organizeand retain information.

The improvements in human cognitive brain functions will typicallyinclude: acquiring information (perception); gathering and selecting(attention); representing and comprehending (understanding); retainingand recalling information (memory); and using recollection to direct andguide behavior (reasoning and coordination of motor outputs).Accordingly, the major result and true effect of orally ingesting theblended supplement is an observable amplification of human brainfunctions and a substantive increase of human concentration, focus andmemory.

The ingestible blended supplement is thus beneficial for andadvantageous to those persons who have a fear or dread (often groundlessand typically unfounded) of a failing memory and/or a loss of mentalalertness and awareness. Consequently, the ingestible blended supplementconcomitantly induces an observable and overt change in human behaviorswhich reflect enhanced cognitive functions and an improved memoryrecall.

Accordingly, among the true benefits and unexpected advantages offeredby the invention is a more favorable perception by the person that hecan focus, concentrate and remember—and thus not only cope but alsosucceed when confronted with and/or subjected to the stresses andproblems of everyday life.

II. DEFINITIONS¹

¹For further explanations and definitional details, please see:

-   -   Goodman & Gillman    -   Saunder's Medical Dictionary    -   Chamber's Technical Dictionary

Although many of the words, terms and titles employed herein arecommonly employed and conventionally understood in their traditionalusage and context by persons ordinarily skilled in this art, a shortlisting of definitions is presented below in order to provide at least aminimal vocabulary of common usage; and to serve as an aid and guide foravoiding misinformation, misunderstandings, and ambiguities in titlesand terminology which often exist in this technical field; and tointroduce specialized terms and particular jargon for recognizing anddistinguishing among the details of the present invention; as well asfor appreciating the true scope and breadth of the claims recitedherein.

The Human Brain: Anatomically, the cerebrum, cerebellum, and medullaoblongata—all of which lie within the cavity space of the cranium.

Human Cognition: The mental processes a human brain uses to organizeinformation. This range of mental processes include acquiringinformation (perception), selecting (attention), representing(understanding) and retaining (memory) information, and using it toguide human behavior (reasoning and coordination of motor outputs).

Human Cognitive Enhancement: The amplification or extension of coremental capacities of the human brain through improvement or augmentationof internal or external information processing systems.

Cognitive Enhancer Agents: A set of often diverse compositions andformulations that can amplify human concentration and increase humanmemory in-vivo.

Nootropic substances: A distinct subset of biochemical entities withinthe Cognitive Enhancer Order of bioactive compositions that arecharacterized by being functionally cognitive enhancing, beingneuroprotective, and being extremely non-toxic in humans in-vivo. Allnootropic substances are by definition cognitive enhancer agents—but notevery cognitive enhancer agent is properly a nootropic substance. Thus,all nootropic substances as a distinct subset of bioactive agents arepurported to be or have been empirically shown to be able to enhancehuman concentration and/or increase human recollection and the formationof memories. Furthermore, all nootropic substances are individually andcollectively functionally capable of crossing the human blood-brainbarrier in-vivo after being introduced as an extraneous agent, andtherein demonstrate their psychoactive properties upon the neurons thenexisting in the human brain.

Agonist: A substance that acts like another chemical composition andtherefore excites or stimulates an action in-vivo. An agonist is aprimary bioactive agent in the dynamic systems of the human body and inits pharmacology; and is the direct opposite of an antagonist.

Neurotransmitter agonist: A bioactive agent which increases theproduction of the neurotransmitter or neurotransmitter precursors in aliving subject in-vivo, and/or increases the number of neurotransmitterreceptors at the synaptic level to increase neurotransmitter expression.

Antagonist: A chemical substance that interferes with the physiologicalaction of another, especially by combining with and blocking its nervereceptor.

Adenosine antagonist: A bioactive agent which decreases or inhibits theexpression of a recognized effect or result of the nucleoside Adenosinein-vivo.

III. THE UNDERLYING PRINCIPLES OF THE INVENTION

The unique concept of the present invention is controlled anddemonstrated by four underlying principles, which are:

The 1^(st) Principle: Five and only five naturally occurringneurotransmitter systems (designated herein as N₁, N₂, N₃, N₄, and N₅respectively) must be involved in order to produce a balancedneuromodulation of the affective neural centers of the brain. Thisprinciple is based on a volume transmission of multiple neurotransmittersystems simultaneously; and also assumes the presence of select neuralcross-communication between different neurotransmitter systems.

It is therefore imperative in this neuromodulation process that all fiveindividual neurotransmitter agent classes be activated togetherconcurrently in order to produce a positive mood enhancement for theperson. As part of this process, if one or more neurotransmitter systemconstituents (N₁ through N₅) are missing, then this omission will causea failure of the blended formulation to initiate positive moodenhancement in-vivo in a consistent and reliable manner.

It is critical to understand and appreciate also that, although morethan sixty neurotransmitter systems are currently known to exist in thehuman body, five and only five naturally occurring neurotransmittersystems (designated as N1, N2, N3, N4, and N5 respectively) are employedby the present invention to produce a balanced neuromodulation of theaffective neural centers of the brain. In particular, no otherneurotransmitter agonistic or antagonistic agents of any kind,functional capacity, chemical composition, or stereochemical structurecan be added nor should be included in the blended formulation as anessential active ingredient at any time, for any purpose. According,there is always a complete absence and lack of any other nootropicneurotransmitter agonist(s) or antagonist(s) except for the requisitefive classes of active ingredient agents, which are overtly limited to:at least one dopamine agonist, a neural stimulant; at least oneacetylcholine agonist, a neural inhibitor; at least one serotoninagonist, a neural inhibitor; at least one GABA agonist, a neuralinhibitor; and at least one adenosine antagonist, a neural stimulant.

The 2^(nd) Principle: It is noted that in order to affect all fiveneuromodulatory systems concurrently, the volume transmission of thefive different classes of neurotransmitter agents is not equalthroughout the human body. Instead, neuromodulation is dominated byinhibitory neurotransmitters system agents such as acetylcholine,serotonin, and gamma aminobutyric acid—thereby producing an overallinhibitory effect (in contrast to an excitatory effect). Consequently,the type number ratio of individual neurotransmitter agent expression isimportant, and the type number ratio of the different classes of agentsmust be tightly controlled in order to produce a positive state of moodenhancement.

The practice and implementation of this 2^(nd) principle is performed inthe following manner: The present invention demands that the properbalance of volume expression of neurotransmitter system agents shouldyield a net balance of zero in order to produce mood enhancement whichis neither excitatory nor inhibitory (i.e., ΔN=0). This principle isdesignated as the Neuromodulary Hypothesis, and is expressed by theformula:

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0

where N_(X) is the net effect of those individual neurotransmittersystem agents which are excitatory/stimulatory (+1, +2, +3 . . . )versus those agents which are inhibitory/relaxant (−1, −2, −3 . . . ) inproducing volume neurotransmission.

As part of this Neuromodulary Hypothesis, if the net balance (ΔN) of allthe individual neurotransmitter system agents present as part of anyformulation is not at parity (ΔN≠0), then an agent imbalance is createdwhich is either stimulatory or inhibitory in effect; and this in turnwill cause a failure to initiate positive mood enhancement in a reliablemanner.

The 3^(rd) Principle: The weight-to-volume ratio of all the individualneurotransmitter system agents is employed to fine-tune thestoichiometric quantities of the discrete nootropic substances in eachadmixture of active ingredients. The weight-to-volume ratio of all theindividual neurotransmitter system agents will reflect specificboundaries and parameters of each blended formulation embodying thepresent invention. Consequently, the weight-to-volume ratio of all theindividual neurotransmitter system agents in any formulation must meetand satisfy specific range limits.

Another aspect of this 3^(rd) principle is that preferred quantities ofindividual neurotransmitter system agents will reflect certain necessaryphysiologic effects associated with a particular neurotransmittersystem. For instance, exceeding a set and limited quantity of specifiednootropic agent may not result in achieving the desired physiologicresult. As one illustration of this point, doubling the amount of anagent N_(X) from 1 to 2 units cannot and does not necessarily producedouble the physiologic effect. Instead, in such instances, it is insteadthe addition of another nootropic agent N_(Y) which acts to augment andincrease the effects of agent N_(X) in a synergistic manner, even withvery small quantity units or doses of the individual agents—therebyresulting in a physiologic result which is greater than the sum of thephysiologic effects of the two individual components N_(X) and N.

The 4^(th) Principle: If nootropic agents components N_(X) and N_(Y) donot result in a symbiotic and synergistic physiologic result which isgreater than the overall effects of using N_(X) and N_(Y) individually,then this outcome will cause a failure of positive mood enhancement tooccur in the person in a consistent and a reliable manner.

Also as a direct corollary, the stoichiometric quantities of the fivedifferent classes of nootropic agents have particular relevance to theefficacy of agent combinations which are synergistic in their effectsdespite having alternative mechanisms of action. For instance,overloading certain neurotransmitter system agents can result in anopposite and wholly unwanted effect, by depleting these brainneurotransmitters over time. Notable examples of this phenomenon includecaffeine, amphetamines, and cocaine.

For these reasons, in the blended formulations of the present invention,the five classes of active ingredient agents are overtly limited to: atleast one dopamine agonist, a neural stimulant; at least oneacetylcholine agonist, a neural inhibitor; at least one serotoninagonist, a neural inhibitor; at least one GABA agonist, a neuralinhibitor; and at least one adenosine antagonist, a neural stimulant.This is represented by a type number ratio of [1:1:1:1:1].

However, a very different type number ratio should be employed in orderto achieve consistent and reliable results in-vivo. Accordingly, therange of truly functional type number ratios starts with a minimal ratioof [2:1:1:1:1] and extends to a maximal ratio of [6:4:3:3:3]. The netphysiologic result of restricting these type number ratios to suchspecified limits is a balanced neurological enhancement.

IV. REQUISITE ACTIVE INGREDIENTS OF THE BLENDED FORMULATIONS

Each and every embodiment of the orally ingestable blended formulationmust comprise not less than five (5) different bioactive ingredients indry or fluid admixture. These five discrete bioactive ingredients are:

(i) At least one naturally existing nootropic dopamine neurotransmitteragonist in a preferred quantity ranging from about 0.01 g to 3.0 g;

(ii) At least one naturally existing nootropic acetylecholineneurotransmitter agonist in a preferred quantity ranging from about 0.01g to 1.5 g;

(iii) At least one naturally existing nootropic serotoninneurotransmitter agonist in a preferred quantity ranging from about 0.01g to 1.6 g;

(iv) At least one naturally existing gamma-aminobutyric acid (GABA)neurotransmitter agonist in a preferred quantity ranging from about 0.01g to 5.0 g; and

(v) At least one naturally existing nootropic adenosine antagonist in apreferred quantity ranging from about 0.01 g to 1.0 g.

Descriptive details for each of these five bioactive ingredients areprovided below.

It is critical to understand and appreciate also that, although morethan sixty neurotransmitter systems are currently known to exist in thehuman body, five and only five naturally occurring neurotransmittersystems (designated as N1, N2, N3, N4, and N5 respectively) are employedby the present invention to produce a balanced neuromodulation of theaffective neural centers of the brain. In particular, no otherneurotransmitter agonistic or antagonistic agents of any kind,functional capacity, chemical composition, or stereochemical structurecan be added nor should be included in the blended formulation as anessential active ingredient at any time, for any purpose. According,there is always a complete absence and lack of any other nootropicneurotransmitter agonist(s) or antagonist(s) except for the requisitefive classes of active ingredient agents, which are overtly limited to:at least one dopamine agonist, a neural stimulant; at least oneacetylcholine agonist, a neural inhibitor; at least one serotoninagonist, a neural inhibitor; at least one GABA agonist, a neuralinhibitor; and at least one adenosine antagonist, a neural stimulant.

1. The Naturally Existing Nootropic Dopamine Neurotransmitter Agonist(s)

In the present invention, naturally occurring nootropic dopamineagonists are employed as one type of active ingredient; and these arebioactive naturally occurring substances that mimic or functionsimilarly to the known neurotransmitter dopamine or those particularcomponents of the central nervous system that use dopamine as a neuralsynapse agent. The attributable effects of dopamine are enhancement ofattention, alertness, and antioxidant activity. Accordingly, eachnootropic dopamine agonist will provide one or more of these wellestablished dopamine functional attributes and capabilities.

Consequently, any and all naturally occurring dopamine neurotransmitteragonists—which are either precursor compounds or are themselves abioactive molecule—are individually and collectively suitable for use asa first essential and critical ingredient in the admixture constitutingthe blended supplement. Among the preferred examples of acceptable andsuitable naturally occurring nootropic dopamine neurotransmitteragonists are: L-phenylalanine; L-tyrosine; N-acetyl-L-tyrosine;L-3,4-dihydroxyphenylalanine (L-DOPA); phenylethylamine;S-adenosyl-methionine; biopterin; amineptine; methylphenidate;selegiline; rasagiline; rhodiola rosea; ropinirole; pramipexole; mucunapruriens; modafinil; and citicoline.

In the expected and intended range of blended formulations, the choicesof these bioactive agents are carefully controlled as to number ofdifferent dopamine neurotransmitter agonists and their individualquantitative amounts. In the preferred embodiments, however, theseparticular agents are expressly limited in both numbers and aliquotamounts; and will be not less than two and not more than six differentnaturally existing nootropic dopamine neurotransmitter agonists in anyprepared admixture of active ingredients. Also when present, eachnootropic dopamine neurotransmitter agonist will appear in an individualquantity ranging from about 100 mg/L to about 6000 mg/L (weight/volume),or alternatively appear in an individual quantity ranging from about 100mg/Kg to about 6000 mg/Kg (weight/weight).

In addition, the particular number of individual nootropic dopamineneurotransmitter agonists present in any blended formulation will beaccounted for as a neurotransmitter replenishment balance factor inorder that the admixture of all essential active agents mathematicallyis zero (“0”) in value. Thus, the actual number of individual nootropicdopamine neurotransmitter agonists then present in any blendedformulation will be chosen carefully and in advance to implement theNeuromodulary Hypothesis described above and expressed by the formula

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0

wherein N₁ is the net effect of those individual dopamineneurotransmitter agonists which are excitatory/stimulatory (+1, +2, +3 .. . ) versus those other agents [N₂+N₃+N₄] which are inhibitory/relaxant(−1, −2, −3 . . . ).

2. The Naturally Existing Nootropic Acetycholine NeurotransmitterAgonist(s)

In the present invention, naturally occurring nootropic acetylcholineagonists are employed as one type of active ingredient; and these arebioactive naturally occurring substances that mimic or functionsimilarly to the known neurotransmitter acetylcholine or thoseparticular components of the central nervous system that useacetylcholine as a neural synapse agent.

Acetylcholine is a facilitator of memory formation; therefore,increasing the availability of this neurotransmitter in the brain willimprove cognitive functions. Accordingly, each nootropic acetylcholineagonist will provide these well established acetylcholine functionalattributes and capabilities.

Consequently, any and all naturally occurring acetylcholineneurotransmitter agonists—which are either precursor compounds or arethemselves a bioactive molecule—are individually and collectivelysuitable for use as a second essential and critical ingredient in theadmixture constituting the blended supplement.

Among the preferred examples of acceptable and suitable naturallyoccurring nootropic acetylcholine neurotransmitter agonists are:choline; 2-dimethylanninoethanol (DMAE); meclofenoxate;alpha-glycerylphosphorylcholine (alpha-GPC); acetylcarnitine;pantothenic acid (Vitamin B₅); galantamine; huperzine A; donepezil;ispronicline; nicotine; and arecoline.

In the expected and intended range of blended formulations, the choicesof these bioactive agents are carefully controlled as to number ofdifferent acetylcholine neurotransmitter agonists and their individualquantitative amounts. In the preferred embodiments, however, theseparticular agents are expressly limited in both numbers and aliquotamounts; and will be not less than one and not more than four differentnaturally existing nootropic acetylcholine neurotransmitter agonists inany prepared admixture of active ingredients. Also when present, eachnootropic acetylcholine neurotransmitter agonist will appear in anindividual quantity ranging from about 250 mg/L to about 2500 mg/L(weight/volume), or alternatively appear in an individual quantityranging from about 250 mg/Kg to about 2500 mg/Kg (weight/weight).

In addition, the particular number of individual nootropic acetylcholineneurotransmitter agonists present in any blended formulation will beaccounted for as a neurotransmitter replenishment balance factor inorder that the admixture of all essential active agents mathematicallyis zero (“0”) in value. Thus, the actual number of individual nootropicacetylcholine neurotransmitter agonists then present in any blendedformulation will be chosen carefully and in advance to implement theNeuromodulary Hypothesis described above and expressed by the formula

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0

wherein N₂ is the net effect of all the individual acetylcholineneurotransmitter agonists which are which are inhibitory/relaxant (−1,−2, −3 . . . ) versus those other agents [N₁+N₅] which areexcitatory/stimulatory (+1, +2, +3 . . . ) in effect.

3. The Naturally Existing Nootropic Serotonin NeurotransmitterAgonist(s)

In the present invention, naturally occurring nootropic serotoninagonists are employed as one type of active ingredient; and these arebioactive naturally occurring substances that mimic or functionsimilarly to the known neurotransmitter serotonin or those particularcomponents of the central nervous system that use serotonin as a neuralsynapse agent.

Serotonin is a neurotransmitter which contributes to human feelings ofwell being and calmness, with possible effects on neurogenesis;therefore, increasing the availability of this neurotransmitter in thebrain will marked improve human mood and observable human cognitivefunctions. Accordingly, each nootropic serotonin agonist will providethese well established serotonin functional attributes and capabilities.

Consequently, any and all naturally occurring serotonin neurotransmitteragonists—which are either precursor compounds or are themselves abioactive molecule—are individually and collectively suitable for use asa third essential and critical ingredient in the admixture constitutingthe blended supplement.

Among the preferred examples of acceptable and suitable naturallyoccurring nootropic serotonin neurotransmitter agonists are:5-hydroxytryptophan (or 5-HTP, 5-hydroxy-L-tryptophan);S-adenosyl-methionine; pyridoxal phosphate (or PLP,pyridoxal-5′-phosphate, P5P, the active form of Vitamin B6); mesembrine;resveratrol; curcumin; piperine; harmal; rhodiola rosea; tianeptine; andL-theanine.

In the expected and intended range of blended formulations, the choicesof these bioactive agents are carefully controlled as to number ofdifferent serotonin neurotransmitter agonists and their individualquantitative amounts. In the preferred embodiments, however, theseparticular agents are expressly limited in both numbers and aliquotamounts; and will be not less than one and not more than three differentnaturally existing nootropic serotonin neurotransmitter agonists in anyprepared admixture of active ingredients. Also when present, eachnootropic serotonin neurotransmitter agonist will appear in anindividual quantity ranging from about 10 mg/L to about 1600 mg/L(weight/volume), or alternatively appear in an individual quantityranging from about 10 mg/Kg to about 1600 mg/Kg (weight/weight).

In addition, the particular number of individual nootropic serotoninneurotransmitter agonists present in any blended formulation will beaccounted for as a neurotransmitter replenishment balance factor inorder that the admixture of all essential active agents mathematicallyis zero (“0”) in value. Thus, the actual number of individual nootropicserotonin neurotransmitter agonists then present in any blendedformulation will be chosen carefully and in advance to implement theNeuromodulary Hypothesis described above and expressed by the formula

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0

wherein N₃ is the net effect of all the individual serotoninneurotransmitter agonists which are which are inhibitory/relaxant (−1,−2, −3 . . . ) versus those other agents [N₁+N₅] which areexcitatory/stimulatory (+1, +2, +3 . . . ) in effect.

4. The Naturally Existing Nootropic Gamma-AminoButyric Acid (GABA)Neurotransmitter Agonist(s)

In the present invention, naturally occurring nootropicgamma-aminobutyric acid (GABA) agonists are employed as one type ofactive ingredient; and these are bioactive naturally occurringsubstances that mimic or function similarly to the knownneurotransmitter gamma-aminobutyric acid (GABA) or those particularcomponents of the central nervous system that use gamma-aminobutyricacid (GABA) as a neural synapse agent.

The gamma-aminobutyric acid (GABA) receptor is an inotropic receptor andligand-gated ion channel; and is a major neurotransmitter in the centralnervous system. Although GABA seems to produce an inhibitory effect onneurotransmitter release, GABA is not an inhibitory neurotransmitteritself—because it stimulates the GABA receptor on the neural cells ofthe brain; and therefore, its direct action and activity is really astimulatory neurotransmitter function in-vivo.

Upon activation, the GABA receptor of the neuron selectively conductschloride ion through its pore, resulting in hyperpolarization of theneuron. This in turn causes an inhibitory effect on neurotransmission bydiminishing the chance of a successful action potential occurring. Mildinhibition of neuronal firing by drugs acting at the GABA receptor ofthe synapse causes a reduction of anxiety (an anxiolytic effect), whilemore pronounced inhibition typically induces general anesthesia.

On this basis therefore, increasing the availability of GABA in thehuman brain will cause a marked improvement of human mood and attitudes;and also induce increases of observable human cognitive functions.Accordingly, each nootropic gamma-aminobutyric acid agonist will providethese well established GABA functional attributes and capabilitiesin-vivo.

Consequently, any and all naturally occurring gamma-aminobutyric acid(GABA) neurotransmitter agonists—which are either precursor compounds orare themselves a bioactive molecule—are individually and collectivelysuitable for use as a fourth essential and critical ingredient in theadmixture constituting the blended supplement.

Among the preferred examples of acceptable and suitable naturallyoccurring nootropic gamma-aminobutyric acid (GABA) neurotransmitteragonists are: ethanol; picrotoxin; and L-theanine.

In the expected and intended range of blended formulations, the choicesof these bioactive agents are carefully controlled as to number ofdifferent gamma-aminobutyric acid (GABA) neurotransmitter agonists andtheir individual quantitative amounts. In the preferred embodiments,however, these particular agents are expressly limited in both theirnumbers and their aliquot amounts; and will be not less than one and notmore than three different naturally existing nootropicgamma-aminobutyric acid (GABA) neurotransmitter agonists in any preparedadmixture of active ingredients. Also when present, each nootropicgamma-aminobutyric acid (GABA) neurotransmitter agonist will appear inan individual quantity ranging from about 10 mg/L to about 5000 mg/L(weight/volume), or alternatively appear in an individual quantityranging from about 10 mg/Kg to about 5000 mg/Kg (weight/weight).

In addition, the particular number of individual nootropicgamma-aminobutyric acid (GABA) neurotransmitter agonists present in anyblended formulation will be accounted for as a neurotransmitterreplenishment balance factor in order that the admixture of allessential active agents mathematically is zero (“0”) in value. Thus, theactual number of individual nootropic gamma-aminobutyric acid (GABA)neurotransmitter agonists then present in any blended formulation willbe chosen carefully and in advance to implement the NeuromodularyHypothesis described above and expressed by the formula

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0

wherein N₄ is the net effect of all the individual gamma-aminobutyricacid (GABA) neurotransmitter agonists which are which areinhibitory/relaxant (−1, −2, −3 . . . ) versus those other agents[N₁+N₅] which are excitatory/stimulatory (+1, +2, +3 . . . ) in effect.

5. The Naturally Existing Adenosine Neurotransmitter Antagonist(s)

In the present invention, naturally occurring nootropic adenosineantagonists are employed as a very different kind of active ingredient;and these are bioactive naturally occurring substances that mimic orfunction similarly to the nucleoside adenosine or those particularcomponents of the central nervous system that use the nucleosideadenosine in-vivo.

The adenosine receptor is one member of the adenosine receptor group ofG protein-coupled receptors which utilizes the nucleoside adenosine asendogenous ligand. Adenosine receptors are implicated in sleep promotionby inhibiting wake-promoting cholinergic neurons in the basal forebrain.

In the human brain, the nucleoside adenosine slows metabolic activity bya combination of different actions. Presynaptically, it reduces synapticvesicle release. Adenosine receptor blockade produces changes inneurotransmitters by stimulating adenosine kinase and adenosinedeaminase—which remove adenosine and prevent it from binding to itsreceptor. These changes after the normal flow of otherneurotransmitters, which in turn then results in major changes to thefunctions of the human central nervous system.

On this basis therefore, markedly decreasing the activity of thenucleoside adenosine in the human brain will cause a marked improvementof human mood and attitudes; and such a reduction of functional activityfor the nucleoside adenosine will correspondingly induce an increase ofobservable human cognitive functions. Accordingly, each nootropicadenosine antagonist will provide these increases of cognitive functionattributes and capabilities in-vivo.

Consequently, any and all naturally occurring nootropic adenosineantagonists—which are either precursor compounds or are themselves abioactive molecule—are individually and collectively suitable for use asa fifth essential and critical ingredient in the admixture constitutingthe blended supplement.

Among the preferred examples of acceptable and suitable naturallyoccurring nootropic adenosine agonists are: caffeine; theophylline;apaxanthine; theobromide; 8-cyclopentyl-1,3-dimethylxanthine (or CPX,8-cyclopentyltheophylline); 8-cyclopentyl-1,3-dipropylxanthine (orDPCPX); 8-phenyl-1,3-dipropylxanthine; bamifylline; and rolofylline.

In the expected and intended range of blended formulations, the choicesof these bioactive agents are carefully controlled as to number ofdifferent nootropic adenosine agonists and their individual quantitativeamounts. In the preferred embodiments, these particular agents areexpressly limited in both numbers and aliquot amounts; and will be notless than one and not more than three different naturally existingnootropic adenosine agonists in any prepared admixture of activeingredients. Also when present, each nootropic adenosine agonist willappear in an individual quantity ranging from about 10 mg/L to about 100mg/L (weight/volume), or alternatively appear in an individual quantityranging from about 10 mg/Kg to about 100 mg/Kg (weight/weight).

In addition, the particular number of individual nootropic adenosineagonists present in any blended formulation will be accounted for as aneurotransmitter replenishment balance factor in order that theadmixture of all essential active agents mathematically is zero (“0”) invalue. Thus, the actual number of individual nootropic adenosineagonists then present in any blended formulation will be chosencarefully and in advance to implement the Neuromodulary Hypothesisdescribed above and expressed by the formula

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0

wherein N₅ is the net effect of all the individual adenosine agonistswhich are excitatory/stimulatory (+1, +2, +3 . . . ) versus those otheragents [N₂+N₃+N₄] which are inhibitory/relaxant (−1, −2, −3 . . . ).

VI. OPTIONALLY PRESENT AND NON-ESSENTIAL INGREDIENTS OF THE BLENDEDSUPPLEMENT

A wide collection and selection of optionally present compounds andcompositions are available as non-compulsory additions and inclusions tospecific formulations of the blended supplements. In each instance,however, these optionally present materials are voluntary choiceadditions; and will appear and exist as non-requisite and freelyelective choice additions to the minimal blended supplement formulationsfor the making of a commercially salable product. It is must always beremembered however, that these non-essential compounds and compositionsare, individually and collectively, always non-mandatory andnoncompulsory; and may be freely employed at will or avoided completelyand entirely.

A variety of discretionary additives and nonobligatory ingredients maybe freely employed as part of the formulation(s) constituting the orallyingestible blended supplement of the present invention. All of these maybe used in the alternative; all are extra and non-compulsory discretecompound and compositions; and all are purely voluntary additions whichmay either be present or be omitted at will.

Optional Non-Essential Ingredient 1 A Flavoring Agent

In general, any type, kind or source of natural fruit flavoring ispreferred and is very desirable for use in the fluid blending of themedicament. In this respect, it is of no importance what the particularflavoring is; or what is the chemical composition of the chosenflavoring; or whether or not the particular flavoring agent is a puresubstance or a impure mixture of multiple compounds; or whether or notthe chosen flavoring agent includes one or more other entities orextraneous substances in addition to the natural flavor extract.

Similarly, it is of no relevance whether the natural flavoring agent isor is not produced in-house by the manufacturer of the medicament; or isobtained as a commercial product made and sold by others. Neither is itmaterial whether or not the flavoring agent is an extract, or aconcentrate, or a distillation; nor whether or not it is in solid orliquid form; nor whether or not it is freshly made, frozen,freeze-dried, evaporated, or condensed. All of these matters are deemedto be matters of commercial cost and/or personal preference.Furthermore, in many use instances, two or more different naturalflavoring agents can and should be used in combination for best results.

It will be recognized also that, if and when it appears prudent to usethem—one or more artificial flavoring agents can be used in place of anatural flavoring agent. The use of artificial flavoring agents,however, is deemed to be a last resort and the least desirable choice.

The proportional ratio range of all the flavoring agents—regardless ofwhether only a single agent is employed or multiple agents incombination are used—can vary in proportional ratio range from as littleas 0.5% (w/v) to as much as 10% (w/v) of the fluid blending. This0.5%-10% (w/v) proportional ratio range, however, is merely the broadestrange deemed to be useful in preparing the medicament. A more desirableproportional ratio range is from about 2.0% to about 8.5% flavoringagent; and a highly preferred proportional ratio range is from about3.3% to about 5.75% (w/v) flavoring agent.

Merely to demonstrate the acceptable range and to illustrate the varietyof suitable natural flavoring agents, the following representativeexamples are provided.

-   -   (i) Fruit flavorings such as peach extracts, pineapple syrups,        apple pie with “crust” extracts, blueberry extracts, raspberry        syrups, lime extracts, black cherry syrups, citric fruit        extracts, and the like.    -   (ii) Maple syrups and molasses.    -   (iii) Mint flavorings such as spearmint and peppermint        concentrates.    -   (iv) Cream, butter, and cheese flavorings.    -   (v) Coffee, tea, and chocolate concentrates.    -   (vi) Vegetable, plant and nut extracts, flavorings or oils.    -   (vii) Candy flavorings.    -   (viii) Liquor extracts and flavorings.    -   (ix) Spices and spice extracts, flavorings, or oils.    -   (x) Vanilla extracts, honey extracts, vinegar extracts, and rose        oil extracts.    -   (xi) Astringency controlling flavors.

Optional Non-Essential Ingredient 2 A Sweetener

It is often preferred that one or more sweeteners be used whenever inthe formulations of the blended supplement; and a wide range and varietyof additional sweeteners are conventionally known and commercially soldtoday for this purpose.

Thus, in any embodiment of the blended supplement, the proportionalratio range of sweetener may vary from as little as about 1.0% (w/v) toas much as about 30% (w/v) of the formulated blending. This 1.0%-30%(w/v) proportional ratio range, however, is merely the broadest rangedeemed to be useful in preparing the medicament. A more desirableproportional ratio range is from about 2% to about 20% sweetener; and ahighly preferred proportional ratio range is from about 5% to about 12%(w/v) sweetener.

Merely illustrating the better-known natural sweeteners commonlyavailable today are the following representative examples: honey;erythritol; sweeteners derived from the Stevia plant; rice syrup;sorghum syrup; sucanat; fructose; agave nectar; barley malt; date sugar;and corn syrup.

Optional Non-Essential Ingredient 3 Minerals

Minerals by broad general definition are used for nutrition; areconsidered to be necessary in limited quantities in the human diet; andas such, are intended to be consumed daily in at least the minimalrecommended doses set forth in the medical and scientific literature.The conventionally recognized common minerals include mineral oxides andpolyoxides; and constitute electrolytes and trace elements of theformulation as a whole.

A modest listing of suitable minerals as optional ingredients includesat least the following: calcium, phosphate, iodine, iron, magnesium, andzinc. Other minerals which are typically present in very small amountsfor health and metabolism are: electrolytes such as sodium, chloride,potassium; trace elements; prosthetic minerals such fluorine, copper,manganese, cobalt, molybdenum, selenium and chromium; and extremely lowconcentrations of metals such as nickel, silicon, vanadium, and tin.

Optional Non-Essential Ingredient 4 Starches and Other Forms of ComplexCarbohydrates

By conventional definition, starch is a polyose found in allassimilating (green) plants. Typically, it is a white hygroscopic powderthat can be hydrolysed to dextrin, which in turn is subsequently tohydrolysed d-glucose. Alternatively, enzymatic digestion of starch withthe enzyme Diatase will yield maltose.

Optional Non-Essential Ingredient 5 Cellulose-Like Biopolymers

The chemical class of cellulose-like biopolymers includespolysaccharides and oligosaccharides; and is exemplified and representedby Chitosan, chitooligosaccharide, chitin, glucosamine, and othersimilar complex sugars. Typifying such substances is Chitosan, acellulose-like biopolymer complex comprised of 6-carbon monosaccharides,whose overall size and molecular weight can vary greatly.

VII. PREFERRED FORMULA REQUIREMENTS AND LIMITATIONS OF THE BLENDEDSUPPLEMENT

The preferred embodiments of the prepared blended formulations areunusually limited in their formulations, and thus are restricted as to:

(i) The ratio proportions of all the individual nootropicneurotransmitter agonists in comparison to all the individual nootropicadenosine antagonists;

(ii) The minimal weight to volume (mg/L) ratio proportions, oralternatively the weight to weight (mg/Kg) ratio proportions, for allthe individual neurotransmitter agonists in comparison to all individualadenosine antagonists; and

(iii) The neurotransmitter replenishment balance factor for theadmixture of essential active agents, which is mathematically must becalculated to be zero (“0”) in value in every instance.

The Singular Ratio Proportion Limitations

In general, the broad parameters for the admixture of essentialbioactive ingredients and their proportional limitations are as follows:

(a) Not less than two and not more than six different naturally existingnootropic dopamine neurotransmitter agonists which are present in atotal quantity ranging from about 100 mg/L to about 6000 mg/L,

(b) Not less than one and not more than four different naturallyexisting nootropic acetylecholine neurotransmitter agonists which arepresent in a total quantity ranging from about 250 mg/L to about 2500mg/L,

(c) At least one and not more than three naturally existing nootropicserotonin neurotransmitter agonists which are present in a totalquantity ranging from about 10 mg/L to about 1600 mg/L,

(d) At least one and not more than three naturally existinggamma-aminobutyric acid (GABA) neurotransmitter agonists which arepresent in a total quantity ranging from about 10 mg/L to about 5000mg/L, and

(e) At least one and not more than three nootropic adenosine antagonistswhich are present in a total quantity ranging from about 10 mg/L toabout 100 mg/L,

wherein the ratio of all individual nootropic neurotransmitter agoniststo all individual nootropic adenosine antagonists is proportionally notless than 7:1 and not more than 16:3, and

wherein the minimal weight to volume (mg/L) ratio for all individualneurotransmitter agonists to all individual adenosine antagonists isproportionally not less than about 30:1, and

wherein the neurotransmitter replenishment balance factor for theadmixture of essential active agents mathematically is zero (“0”) invalue.

It is critical to understand and appreciate also that, although morethan sixty neurotransmitter systems are currently known to exist in thehuman body, five and only five naturally occurring neurotransmittersystems (designated as N1, N2, N3, N4, and N5 respectively) are employedby the present invention to produce a balanced neuromodulation of theaffective neural centers of the brain. In particular, no otherneurotransmitter agonistic or antagonistic agents of any kind,functional capacity, chemical composition, or stereochemical structurecan be added nor should be included in the blended formulation as anessential active ingredient at any time, for any purpose. According,there is always a complete absence and lack of any other nootropicneurotransmitter agonist(s) or antagonist(s) except for the requisitefive classes of active ingredient agents, which are overtly limited to:at least one dopamine agonist, a neural stimulant; at least oneacetylcholine agonist, a neural inhibitor; at least one serotoninagonist, a neural inhibitor; at least one GABA agonist, a neuralinhibitor; and at least one adenosine antagonist, a neural stimulant.

VIII. BLENDING FORMATS FOR AND PHYSICAL STATES OF THE SUPPLEMENT

Alternative formulations of an orally ingestable blended supplement canbe prepared as a dry powder admixture of active ingredients; or in aliquid carrier format, or as a semi-solid hydrogel; and even in solidsuppository form.

Dry Powder Admixtures

Dry admixtures of the five different essential bioactive ingredients canbe prepared at will, with or without inclusion of other solid additives.Such dry admixtures will appear in conventionally known formats such astablets, solid caplets, and hollow gelatin capsules.

In such dry formats, the prepared admixture of active ingredients willexist in powdered or pulverized form and be prepared as either a tablet,or caplet, or as a filled gelatin capsule—which can be swallowed every6-8 hours by the person in accordance with his individual needs; andsuch a dry powder admixture format will provide an orally ingestable,efficacious total daily dosage over every 24 hours.

The manufacture of tablets or capsules containing the appropriateadmixture dosage is conventionally known and is a common mode ofpharmaceutical preparation. Thus, the combination of dry admixture ofactive ingredients with a variety of inert or quiescent biocompatiblesubstances such as corn starch, sweeteners, flavoring agents, minerals,acid buffering agents, and blending agents will yield a range ofdifferent tablets and solid caplets, and gelatin-filled capsules.

Liquid Carriers

The essential purpose and function of a liquid medium or suspensionfluid is to serve as a biocompatible carrier for at least the fiveminimal bioactive and essential ingredients which must be part of everyformulation and embodiment of the orally ingestible blended supplement.Thus, the physical state of the resulting fluid supplement can bealternatively a water soluble blending, or be a water miscible blending,or be a blended aqueous suspension as such. Accordingly, any aqueousbased fluid which is demonstrably non-reactive, non-toxic, andeffectively biochemically neutral in its in-vivo effects is generallysuitable for use when preparing the blended supplement.

In addition, because the formulated supplement is to be orally consumedby the person, the blending need not be prepared in sterile form; and itcan be prepared in advance of use either in bulk form or as single ormultiple dose aliquots; and can typically be stored indefinitely untilneeded by the individual person.

It is most desirable that the fluid carrier of the blended supplement bebiocompatible with the living cells and tissues forming thegastro-intestinal tract and the digestive system of the human body. Thusphysiological strength electrolytes are typically present in the carrierfluid; and fluids such as physiological (0.85%-0.90%) saline and 5%sugar solutions are typically employed as carrier media.

In addition, a broad range of other chemical agents and additives may beincluded in small quantities as optional and non-essential ingredientsin alternative formulations of the fluid carrier. Merely illustratingsuch optional and non-essential ingredients are various minerals, one ormore coloring agents, water soluble natural preservatives, and the like.

Semi-Solid Hydrogels

A hydrogel is a colloidal gel in which water is the primary dispersionmedium. The retention of color, particle identity, and actives areprovided to the hydrogels through the proper selection and combinationof functional polymer, colorant, active ingredient, other functionaladditives, and processing conditions. Proper selection and combinationof the components and processing conditions allow stable semi-solidhydrogels to be formed.

In general, hydrogels do not need to be irradiated with ionizationenergy for the cross-linking effect to be achieved. Suitable functionalpolymers include alginate, gelatin, gluten, starch, agar, xanthan gum,gellan gum, pectin, guar gum, hydroxypropyl methylcellulose (HPMC),methyl cellulose, microcrystalline cellulose, soy protein, whey protein,casein, collagen, hydrolyzed gelatin, and the like. The more preferredmaterials are gelatin, gluten, instant starch, and sodium alginate.

Typically, the amount of functional polymer used in the preparation ofthe hydrogel, before the uptake of water, is from about 1 to about 60weight percent of the material to be extruded. Preferably the amount ofthe functional polymer ranges from about 7 to about 50 weight percent.The polymer used frequently has a molecular weight of less than 250,000daltons, and desirably has a molecular weight of less than 40,000daltons.

Suppositories

Suppositories are water-in-oil emulsions, but exist primarily as soliddosage forms of a medicament intended for administration within anexternally exposed body cavity (such as the rectum or vagina).Suppositories are useful solid drug delivery systems in those situationswhere it is deemed to be difficult or ineffective to deliver medicineorally; and such an alternate route of effective administration thenbecomes necessary and appropriate.

Suppositories are formulated using a mixture of different hydrocarbons(such as petrolatum, mineral oils, fatty acids, triglycerides, fats andlipids) to form a biocompatible solid carrier base; and are compoundedsuch that the shaped solid mass will melt, soften, or dissolve withinthe body cavity where the temperature is around 98.6 degrees F., therebyreleasing the active ingredients contained therein.

Suppository carrier base formulations are stable, nonirritating,chemically neutral, and physiologically inert; and typically utilize avariety of different oily or fatty materials (such as cocoa butter,coconut oil, palm kernel oil, and palm oil) which melt or deform at roomtemperature. Biocompatible carrier base formulations frequently alsocontain various alcohols, surfactants, emulsifiers, and other blendingagents as additives.

IX. ILLUSTRATIVE AND EXEMPLARY FORMULATIONS

The present invention is a non-prescription blended formulation suitablefor oral ingestion by a living human subject, and which after ingestionis able to induce a more positive mood for and to initiate an observableenhancement of cognitive functions in a living human subject.

The intended range and full variety of the blended formulations can andwill take alternative formats. As merely illustrative and exemplary ofthese variants, a minimalist formula, an intermediate formulation, amaximum formula, and a highly preferred blended formulation of essentialactive ingredients is provided below.

It is critical to understand and appreciate also that, although morethan sixty neurotransmitter systems are currently known to exist in thehuman body, five and only five naturally occurring neurotransmittersystems (designated as N1, N2, N3, N4, and N5 respectively) are employedby the present invention to produce a balanced neuromodulation of theaffective neural centers of the brain. In particular, no otherneurotransmitter agonistic or antagonistic agents of any kind,functional capacity, chemical composition, or stereochemical structurecan be added nor should be included in the blended formulation as anessential active ingredient at any time, for any purpose. According,there is always a complete absence and lack of any other nootropicneurotransmitter agonist(s) or antagonist(s) except for the requisitefive classes of active ingredient agents, which are overtly limited to:at least one dopamine agonist, a neural stimulant; at least oneacetylcholine agonist, a neural inhibitor; at least one serotoninagonist, a neural inhibitor; at least one GABA agonist, a neuralinhibitor; and at least one adenosine antagonist, a neural stimulant.

A Minimalist Formulation

A minimalist blended formulation is a controlled admixture of five typesof essential active ingredients, each of which is able to cross theblood-brain barrier in-vivo, wherein the controlled admixture ofessential active ingredients is limited to the following:

(i) only two naturally existing nootropic dopamine neurotransmitteragonists, each of which is present in a quantity ranging from about 0.01g/L to 3.0 g/L,

(ii) only one naturally existing nootropic acetylecholineneurotransmitter agonists, each of which is present in a quantityranging from about 0.01 g/L to 1.5 g/L,

(iii) only one naturally existing nootropic serotonin neurotransmitteragonist present in a quantity ranging from about 0.01 g/L to 1.6 g/L,

(iv) only one naturally existing gamma-aminobutyric acidneurotransmitter agonist present in a quantity ranging from about 0.01g/L to 5.0 g/L,

(v) only one naturally existing nootropic adenosine antagonist presentin a quantity ranging from about 0.01 g/L to 1.0 g/L.

Note also that the “neurotransmitter replenishment balance” of thisminimalist admixture mathematically is [+2−1−1−1+1]=0

and properly conforms to the Neuromodulary Hypothesis expressed by theformula

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0

An Intermediate Formulation

An intermediate blended formulation is also a controlled admixture offive different types of essential active ingredients, each of which isable to cross the blood-brain barrier in-vivo, wherein the controlledadmixture of essential active ingredients is limited to the following:

(a) four different naturally existing nootropic dopamineneurotransmitter agonists which are present in a total quantity rangingfrom about 400 mg/L to about 2,4000 mg/L,

(b) two different naturally existing nootropic acetylecholineneurotransmitter agonists which are present in a total quantity rangingfrom about 500 mg/L to about 5,000 mg/L,

(c) two different naturally existing nootropic serotoninneurotransmitter agonists which are present in a total quantity rangingfrom about 20 mg/L to about 3,200 mg/L,

(d) two different naturally existing gamma-aminobutyric acid (GABA)neurotransmitter agonists which are present in a total quantity rangingfrom about 20 mg/L to about 10,000 mg/L, and

(e) two different naturally existing nootropic adenosine antagonistswhich are present in a total quantity ranging from about 20 mg/L toabout 200 mg/L.

Note also that the “neurotransmitter replenishment balance” of thisintermediate admixture mathematically is [+4−2−2−2+2]=0.

Accordingly, the intermediate blended formulation properly conforms tothe Neuromodulary Hypothesis expressed by the formula

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0

A Maximum Formulation

A maximum blended formulation is also a controlled admixture of fivedifferent types of essential active ingredients, each of which is ableto cross the blood-brain barrier in-vivo, wherein the controlledadmixture of essential active ingredients is limited to the following:

(a) six different naturally existing nootropic dopamine neurotransmitteragonists which are present in a total quantity ranging from about 600mg/L to about 36,000 mg/L,

(b) three different naturally existing nootropic acetylecholineneurotransmitter agonists which are present in a total quantity rangingfrom about 750 mg/L to about 7,500 mg/L,

(c) three different naturally existing nootropic serotoninneurotransmitter agonists which are present in a total quantity rangingfrom about 30 mg/L to about 4,800 mg/L,

(d) three different naturally existing nootropic gamma-aminobutyric acid(GABA) neurotransmitter agonists which are present in a total quantityranging from about 30 mg/L to about 15,000 mg/L, and

(e) three different naturally existing nootropic adenosine antagonistswhich are present in a total quantity ranging from about 30 mg/L toabout 300 mg/L

Note also that the “neurotransmitter replenishment balance” of thisintermediate admixture mathematically is [+6−3−3−3+3]=0.

Accordingly, the intermediate blended formulation properly conforms tothe Neuromodulary Hypothesis expressed by the formula

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0.

A Preferred Formulation

One preferred formulation and the present best embodiment of the blendedsupplement is a fluid preparation which employs a blend of eightindividual nootropic bioactive agents in an isotonic beverage containingabout 7% carbohydrate per liter. This preferred formulation contains thefollowing essential bioactive ingredients.

Quantity Range Compound Name (mg/L) [Type Of Active Agent]L-Phenylalanine (100-3000 mg/L) [a 1^(st) dopamine agonist]Phenylethylannine (100-500 mg/L) [a 2^(nd) dopamine agonist]hydrochloride Mucuna pruriens (50-2500 mg/L) [a 3^(rd) dopamine agonist]Dimethylaminoethanol (100-1500 mg/L) [a 1st acetylcholine agonist]bitartrate Pantothenic acid (10-1000 mg/L) [a 2^(nd) acetylcholineagonist] S-Adenosyl- (100-1600 mg/L) [a single serotonin agonist]methionine tosylate disulfate L-Theanine (100-600 mg/L) [a single GABAagonist] Caffeine, anhydrous (20-600 mg/L) [a single adenosineantagonist]Noteably, in this highly preferred formulation:

(i) There are three different dopamine agonists in the blending.

(ii) The minimal total weight quantity of dopamine agonists (3 differentagents) present per liter is 110 mg, and the maximum total weightquantity of dopamine agonists (3 different agents) present per liter is6000 mg.

(iii) There are two different acetylcholine agonists in the blending.

(iv) The minimal total weight quantity of acetylcholine agonists (2different agents) present per liter is 250 mg, and the maximum totalweight quantity of acetylcholine agonists (2 different agents) presentper liter is 2500 mg.

(v) There is only a single serotonin agonist in the blending.

(vi) L-Theanine is the sole GABA agonist in the blending.

(vii) There is only a single adenosine antagonist in the blending.

(viii) The type number ratio of the five requisite types of activeagents in the blending—i.e., the proportions of individual dopamineagonist/acetylcholine agonist/serotonin agonist/GABA agonist/adenosineantagonist—is 3:2:1:1:1.

(ix) The minimal weight-to-volume ratio for the five types of requisiteactive agents in the blending is 5.0:2.2:2.0:2.0:0.4.

(x) The maximum weight-to-volume ratio for the five types of requisiteactive agents in the blending is 10.0:4.2:3.2:1.0:1.0.

(xi) The neurotransmitter replenishment balance factor for the blendingas a whole mathematically is zero in value, and properly conforms to theNeuromodulary Hypothesis expressed by the formula

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0.

X. THE IN-VIVO METHOD OF TREATMENT The Methodology As a Whole

The present invention provides a method for initiating an improvement ofhuman mood and inducing an observable enhancement of cognitive functionsin a living human subject. This method comprises the following steps:

Step 1: obtaining an orally ingestable non-prescription blendedsupplement comprising a limited admixture of essential bioactive agentsas described previously wherein

(i) the ratio of all individual nootropic neurotransmitter agonists toall individual nootropic adenosine antagonists is proportionally notless than 7:1 and not more than 16:3; and

(ii) the minimal weight to volume (mg/L) ratio for all individualneurotransmitter agonists to all individual adenosine antagonists isproportionally not less than about 30:1, and

(iii) the neurotransmitter replenishment balance for the admixture ofessential active agents mathematically is zero (“0”) in value, andproperly conforms to the Neuromodulary Hypothesis expressed by theformula

ΔN=[N ₁ +N ₂ +N ₃ +N ₄ +N ₅]=0.

Step 2: Orally administering said blended supplement to a living humansubject in a predetermined quantity sufficient to initiate animprovement of human mood and induce an observable enhancement ofcognitive functions in a living human subject.

Step 3: Allowing at least a minimal time period after ingestion for saidorally administered quantity of blended supplement to become assimilatedby and to act within the body of said living human subject. An averagetime period for assimilation is 5-40 minutes; and most typically is lessthan 30 minutes.

Step 4: Periodically monitoring the human subject for objectiveindications of a positive mental state and an observable enhancement ofcognitive functions. Qualitative assessment scores of 0 to 10 (10 beingvery positive feeling of well being) have been reported by testcandidates in empiric studies following an oral intake of the preparedblended formulation as a ingested beverage of 3 drinks during a 48 hourperiod.

Step 5: Determining from said objective indications that a more positivemental state exists and an observable enhancement of cognitive functionshas occurred in the living human subject. Qualitative assessments testedthe prepared blended formulation as an ingested beverage in 200 subjectsand the average resulting score was between 8.0 and 8.5 (10 being verypositive feeling of well being).

Range of Expected Dosages & Frequency of Administrations

The primary and most preferred mode of administration for the blendedsupplement is by simple oral ingestion. To initiate a more favorablestate of mind and to induce an enhancement of cognitive functions, aneffective amount or aliquot for oral intake will vary from about 50 mg(the minimal effective concentration) to not more than 6000 mg (themaximal effective concentration) per day. A highly preferred effectiveconcentration for oral ingestion will range from about 600 mg to about3,000 mg over 24 hours time.

In addition, although the effective oral dosage of blended supplementcan be taken by the person as a single daily administration, it is farmore preferable that the total daily dosage of blended supplement beingested only in part on any given occasion; and that preferably, aseries of 2-5 individual oral administrations of far smaller doses atfixed time intervals be made over each 24 hour time period. In thismanner, a more uniform level of bioactive agents are introduced andpresent within the human body at any given time; and a more consistentefficacious effect is maintained over each 24 hour treatment cycle.

For liquids, about 120-150 ml of blended formulation constitutes asingle dose amount. As a prepared beverage, the 120-150 ml of blendedformulation will contain about 2.5 grams of the five essentialneuroactive agents (excluding sugars, flavorings, etc.). A 3 drink limitover a 24 hour period of time is suggested.

Duration of Induced Effects

The expected duration of induced effects after orally ingesting theblended supplement is expected to be variable among susceptibleindividuals, ranging from 2 or 3 hours to as long as 8 hours, with ahalf life of about 4 hours in typical human subjects. The test subjectwill typically feel effects in less than 30 minutes; and these effectswill last from about 2 to about 8 hours, with an average half life of 4hours. In general therefore, this means that after 4 hours duration,there should be about a 50% reduction in the observed neuroactiveeffects for the person.

Precautions, Contradictions and Side Effects

No side effects at all were encountered by the 200 human test subjectstested. As to possible contraindications, it is advised that thefollowing individuals do not consume this any form of these blendedformulations: Pregnant or nursing women; children less than 13 yearsold; persons who are phenylketonurics; anyone taking MAO inhibitors fordepression; anyone with uncontrolled hypertension and/or cardiaccondition, unless cleared by their doctor. No drug interactions as suchare presently known.

XI. IN-VIVO EXPERIMENTS AND RESULTING EMPIRICAL DATA

To demonstrate the merits and value of the present invention, a varietyof experimental human case studies and resulting empirical data arepresented below. It will be expressly understood, however, that thefacts and data provided below are merely the best evidence of thesubject matter as a whole which is the present invention; and that thesehuman case studies are only illustrative of the full scope of thepresent invention as envisioned and claimed.

A set of clinical trials were performed using the median dosing of a‘typical formulation’ in randomly selected normal, healthy volunteersranging from 14 to 80 years (mean age 44.5 years) greater than 50 kgbody weight over a 10 day period. At the end of the clinical trial,subjects were asked to subjectively rate the feeling of moodenhancement, ranging from a scale of 0 (no change) to 10 (euphoric) andto rate the duration of effect (in hours) following ingestion of theprepared beverage. Members also were encouraged to report any sideeffects, if any.

Test Groupings

Eight different test groups of ten human subjects each (N=10) weredevised as follows:

Test Group 1: Oral solution containing 125 mL juice (7% carbohydrate), 3times daily. This formulation represents placebo.

Test Group 2: L-Phenylalanine, 800 mg and mucina pruriens, 15% L-DOPA,200 mg oral solution in 125 mL juice (containing 7% carbohydrate), 3times daily. This nootropic formulation affects the followingneurotransmitter systems: dopamine agonist, a stimulant. The type numberratio is 2:0:0:0:0 to produce a ΔN=+2. This agent fails the test forproducing predictable mood enhancement because it is has an imbalancedtype number ratio, resulting in a net stimulatory effect (ΔN=+2), andproducing a predictable mood over stimulation.

Test Group 3: Phenylethylamine hydrochloride, 400 mg oral solution in125 mL juice (containing 7% carbohydrate), single dose. This nootropicformulation affects the following neurotransmitter systems: dopamineagonist, a stimulant. The type number ratio is 1:0:0:0:0 to produce aΔN=+1. This agent fails the test for producing predictable moodenhancement because it is has an imbalanced type number ratio, resultingin a net stimulatory effect (ΔN=+1), and producing a predictable moodover stimulation.

Test Group 4: Dimethylaminoethanol bitartrate, 300 mg oral solution in125 mL juice (containing 7% carbohydrate), 3 times daily. This nootropicformulation affects the following neurotransmitter systems:acetylcholine agonist, an inhibitor. The type number ratio is 0:1:0:0:0to produce a ΔN=−1. This agent fails the test for producing predictablemood enhancement because it is has an imbalanced type number ratio,resulting in a net inhibitory effect (ΔN=−1), and producing apredictable mood suppression.

Test Group 5: S-Adenosyl-methionine tosylate disulfate, 300 mg oralsolution in 125 mL juice (containing 7% carbohydrate), 3 times daily.This nootropic formulation affects the following neurotransmittersystems: serotonin agonist, an inhibitor. The type number ratio is0:0:1:0:0 to produce a ΔN=−1. This agent fails the test for producingpredictable mood enhancement because it is has an imbalanced type numberratio, resulting in a net inhibitory effect (ΔN=−1), and producing apredictable mood suppression.

Test Group 6: Anhydrous caffeine, 80 mg oral solution in 125 mL juice(containing 7% carbohydrate), 3 times daily. This nootropic formulationaffects the following neurotransmitter systems: adenosine antagonist, astimulant. The type number ratio is 0:0:0:0:1 to produce a ΔN=+1. Thisagent fails the test for producing predictable mood enhancement becauseit is has an imbalanced type number ratio, resulting in a netstimulatory effect (ΔN=+1), and producing a predictable mood overstimulation.

Test Group 7: L-Theanine, 200 mg oral solution in 125 mL juice(containing 7% carbohydrate), 3 times daily. This nootropic formulationaffects the following neurotransmitter systems: GABA agonist, aninhibitor. The type number ratio is 0:0:0:1:0 to produce a ΔN=−1. Thisagent fails the test for producing predictable mood enhancement becauseit is has an imbalanced type number ratio, resulting in a net inhibitoryeffect (ΔN=−1), and producing a predictable mood suppression.

Test Group 8: Single doses of L-phenylalanine (500 mg), phenylethylaminehydrochloride (400 mg), mucuna pruriens, 15% L-DOPA (200 mg),dimethylaminoethanol bitartrate (200 mg), S-adenosyl-methionine tosylatedisulfate (200 mg), L-theanine (200 mg), and caffeine (80 mg) oralsolution in 125 mL juice (containing 7% carbohydrate). This nootropicformulation affects the following neurotransmitter systems: dopamineagonist, a stimulant; acetylcholine agonist, an inhibitor; serotoninagonist, an inhibitor; GABA agonist, an inhibitor; and adenosineantagonist, a stimulant. The type number ratio is 3:2:1:1:1 to produce aΔN=+3−2−1−1+1=0. The net physiologic result is optimal balanced moodenhancement

Empirical Results

The results in each group are summarized below:

Test Group 1—Score 1.0; marginal effect, lasting about 15 minutes. Noside effects reported.

Test Group 2—Score 4.0; somewhat happy, lasting about 1 to 2 hours. Sideeffects of anxiety and tremors in 3 of 10 subjects.

Test Group 3—Score 7.5; temporary euphoric feeling lasting less than 30minutes. Side effects of flushing in 4 of 10 subjects.

Test Group 4—Score 2.0; mild effect, lasting less than 1 hour. Sideeffects of headache in 1 of 10 subjects.

Test Group 5—Score of 6.0; better mood, lasting 3 hours. No side effectsreported.

Test Group 6—Score of 3.0; felt alert, lasting 2 hours. No side effectsreported.

Test Group 7—Score of 6.5; very calm, sedative-like effect, lasting 3hours. No side effects reported.

Test Group 8—Score of 8.5; euphoric feeling lasting about 30 minutes,followed by a nice aura for about 4 hours. No side effects reported.

RESULTS AND CONCLUSIONS

The results of these preliminary clinical trials present a clinicallysignificant positive mood enhancement in those human test subjects whichreceived a combination of different bioactive agents, in low doseamounts, and which produce a balanced nootropic neurotransmitter effectwhen directly compared to placebo subjects (Test Group 1) andindividuals receiving less than all five types of bioactive agents (TestGroups 2 through 7 respectively).

In addition, with few exceptions, doses of individual constituentsproduced a marginal effect when using three times the dosing quantitywhen compared to the formulation received by Test Group 8 [Single dosesof L-phenylalanine (500 mg), phenylethylamine hydrochloride (400 mg),mucuna pruriens, 15% L-DOPA (200 mg), dimethylaminoethanol bitartrate(200 mg), S-adenosyl-methionine tosylate disulfate (200 mg), L-theanine(200 mg), and caffeine (80 mg) as an oral solution in 125 mL juice(containing 7% carbohydrate)].

The most significant and meaningful clinical effects were seen in testgroups receiving: Phenylethyamine hydrochloride as an active agent,which produced a noticeable but short-term effect of less than 30minutes; and S-adenosyl-methionine tosylate disulfate as an activeagent, which produced moderate mood enhancement but also required 4 to 5times the dosing.

All of the active agents employs as formula constituents have a goodsafety profile, which allows for a large and varied dosing range. Also,toxicity is exceedingly low for the formulated dose limits. Such sideeffects as were reported by a very few test subjects were mild andself-limited, and included only flushing, tremors, anxiety, andheadache. The highly preferred formulation of the blended supplement asa specifically prepared beverage has been tested in over 200 humanvolunteers, without any reported side effects.

The present invention is neither restricted in form nor limited in scopeexcept by the claims appended hereto.

What we claim is:
 1. A method for initiating an improvement of humanmood and inducing an observable enhancement of cognitive functions in aliving human subject, said method comprising the steps of: obtaining anon-prescription blended formulation suitable for oral ingestion by aliving human subject, said blended formulation being a controllednootropic admixture consisting of five different kinds of essentialnootropic active ingredients, each of which is able to pass theblood-brain barrier in-vivo, said controlled nootropic admixture having(a) not less than two different naturally existing nootropic dopamineneurotransmitter agonists, (b) not less than one naturally existingnootropic acetylecholine neurotransmitter agonist, (c) not less than onenaturally existing nootropic serotonin neurotransmitter agonist, (d) notless than one naturally existing nootropic gamma-aminobutyric acid(GABA) neurotransmitter agonist, and (e) at least one nootropicadenosine antagonist, wherein the ratio of all individual nootropicneurotransmitter agonists to all individual nootropic adenosineantagonists is proportionally not less than 5:1, and wherein theneurotransmitter replenishment balance for the admixture of essentialactive agents mathematically is zero (“0”) in value, and wherein thereis a complete absence of any other kind of nootropic agonist orantagonist; orally administering said blended formulation to a livinghuman subject in a predetermined quantity sufficient to initiate animprovement of human mood and induce an observable enhancement ofcognitive functions in a living human subject; allowing at least aminimal time period after ingestion for said orally administeredquantity of blended formulation to become assimilated by and to actwithin the body of said living human subject; periodically monitoringthe human subject for objective indications of a positive mental stateand an observable enhancement of cognitive functions; and determiningfrom said objective indications that a more positive mental state existsand an observable enhancement of cognitive functions has occurred in theliving human subject.
 2. A method for initiating an improvement of humanmood and inducing an observable enhancement of cognitive functions in aliving human subject, said method comprising the steps of: obtaining anon-prescription blended formulation suitable for oral ingestion by aliving human subject, said blended formulation being a controllednootropic admixture consisting of five different kinds of essentialnootropic active ingredients, each of which is able to pass theblood-brain barrier in-vivo, said controlled nootropic admixture having(a) not less than two and not more than six different naturally existingnootropic dopamine neurotransmitter agonists, (b) not less than one andnot more than four naturally existing nootropic acetylecholineneurotransmitter agonists, (c) not less than one and not more than threenaturally existing nootropic serotonin neurotransmitter agonists, (d)not less than one and not more than three naturally existing nootropicgamma-aminobutyric acid (GABA) neurotransmitter agonists, and (e) atleast one and not more than three nootropic adenosine antagonists,wherein the ratio of all individual nootropic neurotransmitter agoniststo all individual nootropic adenosine antagonists is proportionally notless than 5:1 and not more than 16:1, and wherein the neurotransmitterreplenishment balance for the admixture of essential active agentsmathematically is zero (“0”) in value, and wherein there is a completeabsence of any other kind of nootropic agonist or antagonist; orallyadministering said blended formulation to a living human subject in apredetermined quantity sufficient to initiate an improvement of humanmood and induce an observable enhancement of cognitive functions in aliving human subject; allowing at least a minimal time period afteringestion for said orally administered quantity of blended formulationto become assimilated by and to act within the body of said living humansubject; periodically monitoring the human subject for objectiveindications of a positive mental state and an observable enhancement ofcognitive functions; and determining from said objective indicationsthat a more positive mental state exists and an observable enhancementof cognitive functions has occurred in the living human subject.
 3. Themethod recited in claim 1 or 2 whereby a series of distinct biochemicalchanges are caused in the living human subject.
 4. The method recited inclaim 3 whereby concurrent stimulation of dopamine, serotonin, GABA, andacetylcholine receptors, with simultaneous reversible adenosine receptorblockade, is caused in-vivo.
 5. The method recited in claim 1 or 2whereby psychological consequences are initiated in the living humansubject.
 6. The method recited in claim 5 wherein said psychologicalconsequences initiated in the living human subject are at least oneselected from the group consisting of inducing a positive change inone's personal perceptions, evoking optimism as the subjective state ofmind, and eliciting a more sociable attitude.
 7. The method recited inclaim 1 or 2 whereby improvements in human cognitive brain functions arefound in the living human subject.
 8. The method as recited in claim 7wherein said improvements in human cognitive brain functions found inthe living human subject are at least one selected from the groupconsisting of acquiring information, gathering and selecting,representing and comprehending, retaining and recalling information, andusing recollection to direct and guide behavior.
 9. The method recitedin claim 1 or 2 whereby an amplification of human concentration and anincrease of human memory are instituted in the living human subject. 10.The method recited in claim 1 or 2 wherein said orally administeredblended formulation becomes assimilated and acts within the body of theliving human subject within 5-40 minutes time.
 11. The method recited inclaim 1 or 2 wherein said periodic monitoring of the living humansubject for objective indications of a positive mental state and anobservable enhancement of cognitive functions is made by qualitativeassessment scoring.
 12. The method recited in claim 1 or 2 wherein saiddetermining from objective indications that a more positive mental stateexists and an observable enhancement of cognitive functions has occurredin the living human subject is made by qualitative assessment testing.13. The method recited in claim 1 or 2 wherein the expected duration ofinduced effects ranges from about 2 to about 8 hours.
 14. The methodrecited in claim 1 or 2 wherein the age of the living human subjectranges from 14 to 80 years.